Avian influenza H7N9 virus evolution: defining the impact of internal genes on virus infection in avian and mammalian species

Lead Research Organisation: The Pirbright Institute
Department Name: Avian Influenza

Abstract

In nature, many distinct subtypes of avian influenza (AI) viruses circulate in wild aquatic birds with no consequence to farmed poultry or human health. However, on occasion, these viruses infect domesticated poultry and undergo genetic changes that sometimes result in the emergence of novel viruses with unforeseen biological and pathological characteristics. In recent years, a number of novel AI viruses including H5N1, H5N2, H5N8, H7N1, H7N2, H7N3, H7N7, H7N9, H9N2 and H10N8 have emerged in poultry. H5N1 and H9N2 strains have, within a short space of time, spread to many countries globally, inflicting enormous economic losses together with zoonotic infections of humans with fatal outcomes.

In 2013, a novel H7N9 AI virus strain emerged in poultry in China and caused a localized epidemic in humans. The virus is characterised as having a low pathogenicity phenotype and causes subclinical disease and no mortality in chickens. However, human contact with infected birds has led to sporadic severe disease in humans and over 180 fatalities. The virus is now enzootic in poultry in China and possibly other neighboring regions. In order to reduce its zoonotic impacts, large scale culling of infected and potential contact poultry flocks is being carried out in China, with losses so far amounting to over $6.5 billion and predicted to increase substantially. These pre-emptive control measures have become less effective as the spread of the virus in birds widens. The virus continues to evolve and new reassortant genotypes are emerging, carrying genes of other co-circulating poultry influenza virus strains. This exceptionally rapid evolution may potentially drive further increases in virus infectivity, transmissibility and virulence for both poultry and humans; posing great threats to global food security, animal and public health, socioeconomic wellbeing and the environment.

Considering the emerging and potentially global consequences of this novel H7N9 virus, there is an urgent need to bring this virus under control, reduce its prevalence in the environment and halt its spread to humans. Developing such control measures requires a comprehensive knowledge base about the nature of infecting virus, such as the viral factors that allow cross-species infection, the rates and mechanism of transmission between birds and from birds to humans and the genetic determinants of virulence in mammalian species compared to birds.

The proposed research aims to gain insight into the viral factors that are contributing to the emergence and spread of novel H7N9 virus within poultry, and its transmission to and pathogenicity in humans (using a well-characterised ferret model for human infection). We will also assess the potential threat presented by virus strains that could emerge by similar reassortment events in the future. This project will investigate: (i) how does the internal H9N2 gene cassette change the virological properties of H7N9 influenza virus?; (ii) how do internal gene cassettes from diversified clades of H9N2 viruses impact on H7N9 virus pathogenesis and transmission in avian and mammalian species?; and (iii) how do the H7N9 viruses transmits from poultry to humans?

The linking of identified genetic signatures associated with cross-species transmission and virulence with publically available virus genetic data will ultimately help to better predict potential immediate threats. The knowledge gained during this study will enable the design and development of improved tailor-made tools including vaccines, diagnostic reagents and antivirals allowing better control and management of AI infections. Improved control measures together with offering direct benefits may also provide substantial indirect economic, public health, environmental and social benefits to wider communities on both the national and global scale.

Technical Summary

The emergence of a novel genotype of H7N9 virus threatens human and animal health, global food security and world economies. In order to minimize these impacts, a complete understanding is required of the biological properties of the current and predicted future H7N9 reassortant viruses including virus infectivity, host tissue tropism, cross-species transmission and pathogenesis. This project will investigate the genetic parameters that contribute to H7N9 virus maintenance in poultry and transmission to humans. To address this, advanced molecular virology and animal infection studies will be performed. A series of H7N9 viruses will be generated using reverse genetics that represent circulating viruses in poultry, and some human infection isolates. Due to rapid reassortment with other H9N2 viruses, recombinant viruses that carry H9N2 internal genes of representative current prevalent strains in poultry of different geographical regions will also be generated. A detailed assessment of infectivity and replication of the recombinant viruses using established in vitro virus infection assays will be performed. Viruses exhibiting marked differential biological behavior in vitro will be further evaluated for their pathogenicity and transmissibility in chickens and ferrets (a well characterised model for human influenza infection). The likelihood of increased inter-species transmission of viruses by the airborne route will also be investigated. The air flow from the isolation unit that house the infected chickens will be diverted towards the isolation unit that house uninfected ferrets. Infection parameters such as clinical signs, virus shedding and, in the case of severe disease, post mortem and histopathological findings will provide evidence of virus transmission via air. These approaches ultimately will allow systematic dissection of viral genetic components directly impacting on H7N9 virus tissue tropism, pathogenesis, and transmission in avian and mammalian species.

Planned Impact

We have seen the global impacts of high pathogenicity avian influenza (AI) viruses. In addition, the recent emergence and enzootic spread of a novel H7N9 virus in China has further threatened poultry production systems, human health, food security, trade and the economy. H7N9, being a low pathogenicity virus, does not cause apparent disease in chickens but handling of infected birds has resulted in fatal human disease. The enormous impact of AIV on poultry production, trade and livelihood of millions of poor farmers and shop keepers is incalculable due to control measures, such as large scale culling of infected and at risk poultry flocks and closing down poultry trade markets and allied poultry industries. However, these pre-emptive measures were unable to prevent the virus becoming enzootic in poultry in China. New and improved tools are most certainly required to control and eradicate such viruses and their development and deployment will require an in-depth understanding of the viral factors driving virus persistence in chickens and transmission to humans.

This programme of research will generate and deliver knowledge that will directly impact on AI disease control systems globally. We will undertake integrated and innovative approaches that will analyse the virological parameters leading to H7N9 virus emergence. We will advance the fundamental understanding of influenza evolution, spread and virulence in poultry and humans. Thus, the research will directly benefits human and animal health, the poultry industry and the general public. The objectives of this project are directly aligned with the strategic priorities of BBSRC and other national and international organizations having an interest in disease control including; MRC, Defra, World Organisation for Animal Health (OIE), World Health Organization (WHO), Food and Agriculture Organization of the United Nations (FAO).

The research will harness the collaborative efforts and expertise of UK scientists working to improve the control of AIV for sustainable growth of the poultry industry and reduction of zoonotic infection risks. The research will also enhance research capacity and training of the next generation of scientists for multi-disciplinary research that addresses priority concerns of infectious diseases on global health and food security.

The outcomes of this research will be communicated to stakeholders via multiple mechanisms including publication of the outcomes on publically available open access information sharing systems. Information will be shared promptly via peer-reviewed open access journals, presentations at conferences and workshops helping to determine the research directions and priorities by the learned societies and funding bodies. The engagement with policy makers and disease control agencies will allow making informed decisions and developing effective strategies to combat the increasing number of emerging AI viruses.

The PIs also have experience collaborating with potential beneficiaries outside the immediate academic community, including governmental and non-governmental organizations and the corporate sector. Scientific staff and collaborators involved in the project will exploit as many opportunities as possible to disseminate the research for wider public benefits. This will be achieved by utilising well-established public engagement platforms such as BBSRC Business, periodic global animal health, zoonotic diseases impacting public health and food security teleconference. Staff involved in this project will also be encouraged to be STEM (Science, Technology, Engineering and Mathematics) ambassadors and participate in STEM activities.

Publications

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.Baron M (2018) Recent advances in viral vectors in veterinary vaccinology in Current Opinion in Virology

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Ali M (2019) Avian Influenza A(H9N2) Virus in Poultry Worker, Pakistan, 2015. in Emerging infectious diseases

 
Description This project is just initiated and we are evaluating the potential risks of novel H7N9 genotypes emerging through genetic re-assortment with H9N2 viruses to the poultry industry and global human health.

The research has examined the H7N9 virus infectivity and replication in vitro in cultured cells and experiments are underway to determine how internal genes of H7N9 virus derived from H9N2 viruses contributing in virus replication, virulence and transmission in chickens and humans.

New research method entitled" A restriction digestion and ligation independent technique for cloning influenza gene segments into pHW2000" was developed that allow efficient cloning of polymerase genes of influenza viruses for generation of recombinant influenza viruses using reverse genetic technique.

We identified that co-infection of low pathogenicity H9N2 and H7N9 viruses in ovo (in embryonated hen eggs) or in vivo (in infected chickens) results in the emergence of novel strains of H7N9, H9N9 and H9N2 reassortant viruses with increased pathogenicity and transmissibility in chickens.

Avian influenza H7N9 virus emerged in humans in 2013 and has continued to cause outbreaks in China. We have isolated and characterized 73 H7-reactive monoclonal antibodies from peripheral B cells from four donors infected in 2013 and 2014. Crystal structures of three neutralizing and protective antibodies in complex with the H7 haemagglutinin revealed that they recognize overlapping residues surrounding the receptor-binding site of haemagglutinin. One of the antibodies, L4A-14, bound into the sialic acid binding site and made contacts with haemagglutinin residues that were conserved in the great majority of 2016-2017 H7N9 isolates.

The Global Alliance for Research on Avian Diseases 2018, International Conference, January 17 to 19, 2018, Hanoi, Vietnam, attended by over 150 delegates from academia, poultry breeding/farming, and the pharmaceutic industry, discussed the major challenges and research advances related to the control of poultry diseases. The topics reviewed included the continuous threat from avian influenza and its antigenic shifts/drifts, the risks of disease transmission within and from live bird markets, the challenges from antigenic diversity of other avian viruses, innovative approaches for poultry vaccine development, and the potential opportunities to introduce genetic resistance to infectious agents through novel gene-editing techniques.

Significant new knowledge has been generated regarding the influenza virology that will guide risk assessment of emerging novel genotypes that could be of increased zoonotic potential. Some of the research outputs are being translated into publications. The outputs include (i) development of new research methodology that will improve the reverse genetics system of the avian influenza virus; (ii) generation of new research questions regarding the host range and transmission of avian influenza viruses; (iii) development of new collaborations with UK and international researchers working on viral diseases affecting animals and humans (iv) development of UK skill-base on animal virology and immunology; the researchers gained training for working in the high containment laboratory for undertaking research on highly infectious zoonotic and pandemic viruses; (v) enhancement of interpersonal skills of early-career researchers (postdoctoral and PhD students) via attending conferences and workshops for becoming next-generation research leaders.
Exploitation Route The work has been presented in scientific meetings and to our collaborators. We and researchers around the world will use our findings and methods to improve control systems against influenza viruses. The outputs of the project entitled "A restriction digestion and ligation independent technique for cloning influenza gene segments into pHW2000" was presented at Global Alliance for Research on Avian Diseases (GARAD) Conference held at Fortuna Hotel Hanoi, Vietnam 17-19 January 2018.

Part of the outcomes of this project were presented at the meeting with key animal health stakeholders in the UK. The presentation title "Understanding avian influenza virus evolution and development of next-generation vaccines was presented at 459th Scientific Meeting of The Veterinary Research Club at The Farmers Club, 3 Whitehall Court London, 14th February 2020.
Sectors Agriculture, Food and Drink,Creative Economy,Environment,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description The work has been presented in scientific meetings. We and other researchers around the world will use our findings and methods to improve control systems against influenza viruses. A new method entitled 2A restriction digestion and ligation independent technique for cloning influenza gene segments into pHW2000" was developed and presented at the Global Alliance for Research on Avian Disease-2018 (GARAD-2018) Conference held at Fortuna Hotel, Hanoi, Vietnam 17-19 January 2018. The research identified factors that aid the virulence and persistence of avian influenza viruses in different animals and bird species. The outcome of this research directly feeds into surveillance and risk assessment of emerging and re-emerging viruses, enabling the implementation of rapid and appropriate disease mitigation strategies. Delegates actively debated the challenges, priorities, and opportunities for academia in driving avian disease research, the importance of developing improved disease measures by industry, and the contribution by the farming sector in the low- and middle-income countries. Because of the global nature of these diseases, it is of vital importance to work collaboratively to generate effective mitigation opportunities via innovative strategies. This study has emphasized the need for updated H7N9 vaccines. We have shown that humans naturally infected with H7N9 influenza make an antibody response that includes rare broadly neutralizing and highly protective antibodies that bind the receptor-binding region of the H7 haemagglutinin, and common non-neutralizing antibodies, many of which cross-react with H3 haemagglutinin, and which may also be protective, at least in prophylaxis. H7N9 infection and vaccination are expanding similar repertoires of B cells which bodes well for the development of effective antibody-inducing vaccines. Our study evaluated the consequences of reassortment between the H7N9 and the contemporary H9N2 viruses of G1 lineage that are enzootic in poultry across the Indian sub-continent and the Middle East. Co-infection of chickens with these viruses resulted in the emergence of novel reassortant H9N9 viruses with genes derived from both H9N2 and H7N9 viruses. Our work provides potential risks posed by the emerging novel viruses (H9N9) due to reassortment. The research outputs were published in 2022, entitled "Co-infection of chickens with H9N2 and H7N9 avian influenza viruses leads to the emergence of the reassortant H9N9 virus with increased fitness for poultry and zoonotic potential. Journal of Virology. https://doi.org/10.1128/jvi.01856-21.
First Year Of Impact 2022
Sector Agriculture, Food and Drink,Creative Economy,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic,Policy & public services

 
Description BBSRC International Partnering Awards
Amount £49,500 (GBP)
Funding ID BB/P025803/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 07/2017 
End 07/2021
 
Description Commonwealth Scholarship. Molecular determinants impacting avian influenza H9N2 virus evolution, replication fitness and virulence
Amount £200,000 (GBP)
Funding ID LKCS-2019- 665 
Organisation British Council 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2019 
End 10/2022
 
Description Enhancing protective efficacy of avian influenza vaccines through targeted delivery of protective antigens to chicken immune cells
Amount £98,212 (GBP)
Funding ID BB/R50595X/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2017 
End 09/2021
 
Description Institutional Links grants
Amount £269,123 (GBP)
Funding ID 261727271 
Organisation Newton Fund 
Sector Public
Country United Kingdom
Start 07/2017 
End 07/2019
 
Description Japan Partnering Award
Amount £49,500 (GBP)
Funding ID BB/P025803/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2017 
End 08/2021
 
Description Newton Institutional Links grant
Amount £269,123 (GBP)
Funding ID 261727271 
Organisation Newton Fund 
Sector Public
Country United Kingdom
Start 08/2017 
End 08/2019
 
Description Pirbright Institute Flexible Talent Mobility Account
Amount £180,000 (GBP)
Funding ID BB/S507945/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 11/2018 
End 03/2021
 
Description Reducing the Economic and Zoonotic Impact of Avian Influenza (REZIAI): delivering novel vaccines and diagnostics from laboratory to the field.
Amount £400,000 (GBP)
Funding ID BB/S013792/1 
Organisation The Pirbright Institute 
Sector Academic/University
Country United Kingdom
Start 02/2019 
End 01/2021
 
Description The Global Challenges Research Fund
Amount £640,473 (GBP)
Organisation Research Councils UK (RCUK) 
Sector Public
Country United Kingdom
Start 03/2019 
End 03/2024
 
Description iCASE studentship: Production and assessment of antiviral prophylactic properties of natural biomolecules against avian influenza and Newcastle disease viruses affecting poultry
Amount £100,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2019 
End 09/2023
 
Title A ligation and restriction enzyme independent cloning technique: an alternative to conventional methods for cloning hard-to-clone gene segments in the influenza reverse genetics system 
Description we developed an easy and efficient ligation and restriction enzyme independent (LREI) cloning method for cloning influenza gene segments into pHW2000 vector. The method involves amplification of megaprimers followed by PCR amplification of megaprimers using a bait plasmid, DpnI digestion and transformation. ligation and restriction enzyme independent (LREI) cloning method represents an alternative strategy for cloning influenza gene segments that have internal restriction sites for the enzymes used in reverse genetics. Further, the problem of genetic instability in bacteria can be alleviated by growing recombinant bacterial cultures at a lower temperature. This technique can be applied to clone any influenza gene segment using universal primers, which would help in the rapid generation of influenza viruses and facilitate influenza research and vaccine development. 
Type Of Material Technology assay or reagent 
Year Produced 2020 
Provided To Others? Yes  
Impact The method will help in the rapid generation of reverse genetic base influenza viruses and facilitate influenza research and vaccine development. 
URL https://virologyj.biomedcentral.com/articles/10.1186/s12985-020-01358-2
 
Title Detection of HA antigens of avian influenza viruses 
Description Assay for detection of recombinant HVT expressing HA antigens of avian influenza viruses 
Type Of Material Technology assay or reagent 
Year Produced 2018 
Provided To Others? Yes  
Impact This new method will help to detect recombinant HVT vaccine expressing HA antigen in infected cell. 
 
Title ELISA and next generation sequencing of whole genome of influenza viruses at Oxford University Clinical Research Unit in Vietnam (OUCRU) Hanoi, Vietnam. 
Description 1. Reagents (recombinant HA and NP proteins) and monoclonal antibodies were provide to OUCRU_ Vietnam for for establishment of serological and genomic assessment of diversity of influenza virus infections in Human and animals. 
Type Of Material Technology assay or reagent 
Year Produced 2016 
Provided To Others? Yes  
Impact We this project help, The OUCRU-VN are established a permanent facility to undertake NGS analysis and serlogical analysis of avain influenza viruses. 
 
Description Avian influenza H7N9 virus evolution: defining the impact of internal genes on virus infection in avian and mammalian species 
Organisation Animal and Plant Health Agency
Country United Kingdom 
Sector Public 
PI Contribution Provision of samples and reagents for research
Collaborator Contribution Provision of samples, reagents for research and research facilities
Impact Research output entitled "A restriction digestion and ligation independent technique for cloning influenza gene segments into pHW2000" was presented at January 17th to 19th 2018. Fortuna Hotel, Lang Ha Street, Hanoi, VietNam (Presented by postdoctoral scientist Dr Sushant Bhat
Start Year 2016
 
Description Avian influenza H7N9 virus evolution: defining the impact of internal genes on virus infection in avian and mammalian species 
Organisation Francis Crick Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution (1) Exchange of research methods and reagents
Collaborator Contribution (1) Exchange of research methods and reagents. (2) Provision of training to PhD students and postdoctoral Scientist (3) Critical review of experimental data and manuscripts.
Impact (1) Joint funding: BBSRC Newton Fund: UK-China-Philippines-Thailand Swine and Poultry Research Initiative (2018-2021). Understanding antigenic diversity, zoonotic potential and immunological prevention of avian influenza viruses affecting poultry. Value: £497,995.93. UK Co-Is: Prof John McCauley (Crick Institute), Dr Richard Reeve (University of Glasgow). Collaborators from China: Dr Yipeng Sun, Prof Jinhua Liu and Dr Juan Pu (China Agricultural University), Prof Yongqing Li (Beijing Academy of Agriculture and forestry Sciences), Dr Wenfei Zhu (National Institute for Viral Disease Control and Prevention, China CDC).
Start Year 2007
 
Description BBSRC - Oxford University iCASE Studentship (October 2019- September 2023). Production and assessment of antiviral prophylactic properties of natural biomolecules against avian influenza and Newcastle disease viruses affecting poultry production 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution This collaboration between The Pirbright Institute (UK), Oxford University (UK) and industrial partners in Italy. This project will conceived and developed bu MI. The PhD student (Holly Everest) in my group is investigating the antiviral prophylactic properties of natural biomolecules against avian influenza and Newcastle disease viruses affecting poultry production.
Collaborator Contribution The partners in Italy will produce and purify natural antiviral molecules effective against avian influenza and other poultry viruses.
Impact This project started in January 2020.
Start Year 2020
 
Description Collaboration on the development of intranasal live-attenuated vaccine against SARS-CoV-2 
Organisation Lancaster University
Country United Kingdom 
Sector Academic/University 
PI Contribution Contributed reagents to tests the immunogenicity and protective efficacy of an intranasal live-attenuated vaccine against SARS-CoV-2 in preclinical animal models including mice and hamster.
Collaborator Contribution The partners undertook most of the work to complete the study detailed in the publication entitled "Immunogenicity and protective efficacy of an intranasal live-attenuated vaccine against SARS-CoV-2 in preclinical animal models". https://www.biorxiv.org/content/10.1101/2021.01.08.425974v1 Abstract of publication. The global deployment of an effective and safe vaccine is currently a public health priority to curtail the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we evaluated a Newcastle disease virus (NDV)-based intranasal vectored-vaccine in mice and hamsters for its immunogenicity, safety and protective efficacy in challenge studies with SARS-CoV-2. The recombinant (r)NDV-S vaccine expressing spike (S) protein of SARS-CoV-2 administrated via intranasal route in mice induced high levels of SARS-CoV-2-specific neutralizing immunoglobulin A (IgA) and IgG2a antibodies and T cell-mediated immunity. Hamsters vaccinated with two doses of vaccine showed complete protection from clinical disease including lung infection, inflammation, and pathological lesions after SARS-CoV-2 challenge. Importantly, a single or double dose of intranasal rNDV-S vaccine completely blocked SARS-CoV-2 shedding in nasal turbinate and lungs within 4 days of vaccine administration in hamsters. Taken together, intranasal administration of rNDV-S has the potential to control infection at the site of inoculation, which should prevent both the clinical disease and transmission to halt the spread of the COVID-19 pandemic.
Impact The partnership resulted in a joint publication. "Immunogenicity and protective efficacy of an intranasal live-attenuated vaccine against SARS-CoV-2 in preclinical animal models". https://www.biorxiv.org/content/10.1101/2021.01.08.425974v1 Abstract of publication. The global deployment of an effective and safe vaccine is currently a public health priority to curtail the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we evaluated a Newcastle disease virus (NDV)-based intranasal vectored-vaccine in mice and hamsters for its immunogenicity, safety and protective efficacy in challenge studies with SARS-CoV-2. The recombinant (r)NDV-S vaccine expressing spike (S) protein of SARS-CoV-2 administrated via intranasal route in mice induced high levels of SARS-CoV-2-specific neutralizing immunoglobulin A (IgA) and IgG2a antibodies and T cell-mediated immunity. Hamsters vaccinated with two doses of vaccine showed complete protection from clinical disease including lung infection, inflammation, and pathological lesions after the SARS-CoV-2 challenge. Importantly, a single or double dose of intranasal rNDV-S vaccine completely blocked SARS-CoV-2 shedding in nasal turbinate and lungs within 4 days of vaccine administration in hamsters. Taken together, intranasal administration of rNDV-S has the potential to control infection at the site of inoculation, which should prevent both the clinical disease and transmission to halt the spread of the COVID-19 pandemic.
Start Year 2020
 
Description Commonwealth Scholarship. Molecular determinants impacting avian influenza H9N2 virus evolution, replication fitness and virulence 
Organisation Royal Veterinary College (RVC)
Country United Kingdom 
Sector Academic/University 
PI Contribution I develop a research project proposal in which we are investigating how evolutionary changes in the H9N2 avian influenza virus modulate virus fitness and virulence in chickens. This PhD studentship project was funded by Commonwealth scholarship commission for 3 years.
Collaborator Contribution The collaborating Partner Dr Nicola Lewis at Royal Veterinary College is a co-supervisor of the PhD student Thusitha Karunarathna. she provide necessary guidance to achieve prescribed objectives of this project.
Impact The project is at its initial stage.
Start Year 2019
 
Description Development of novel diagnostic tools and vaccines 
Organisation Francis Crick Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution The outcomes of research led to incite new collaborations with following partners in UK, Vietnam and Pakistan. Together with partners we apply for the collaborative research grant to BBSRC entitled "Combating avian influenza through systematic analysis of antigenic drift, genetic variation, and development of novel diagnostic tools and vaccines". That led to further improvement avian influenza virus vaccines and diagnostics and a number of research publication.
Collaborator Contribution The partners are evaluating the potency and efficacy of vaccines in countries where the disease is enzootic in poultry.
Impact 1. Peacock TP, Benton DJ, Sadeyen J-R, Chang P, Sealy JE.,d, Bryant JE, Martin SR., Shelton H, McCauley JW, Barclay WS, Iqbal M (2017) Variability in H9N2 haemagglutinin receptor binding preference and pH of fusion. Emerging Microbes & Infections 6, e11 2. Peacock T, Reddy K, James J, Adamiak B, Barclay W, Shelton H, Iqbal M (2016). Antigenic mapping of an H9N2 avian influenza virus reveals two discrete antigenic sites and a novel mechanism of immune escape. Scientific Reports 5: 18745. doi: 10.1038/srep18745. 3. Thuy DM, Peacock TP., Bich VTN, . Iqbal M, Juliet E. Bryant (2016). Prevalence and diversity of H9N2 avian influenza in chickens of Northern Vietnam, 2014. Infection, Genetics and Evolution 44: 530-540
Start Year 2014
 
Description Development of novel diagnostic tools and vaccines 
Organisation Imperial College London
Department School of Public Health
Country United Kingdom 
Sector Academic/University 
PI Contribution The outcomes of research led to incite new collaborations with following partners in UK, Vietnam and Pakistan. Together with partners we apply for the collaborative research grant to BBSRC entitled "Combating avian influenza through systematic analysis of antigenic drift, genetic variation, and development of novel diagnostic tools and vaccines". That led to further improvement avian influenza virus vaccines and diagnostics and a number of research publication.
Collaborator Contribution The partners are evaluating the potency and efficacy of vaccines in countries where the disease is enzootic in poultry.
Impact 1. Peacock TP, Benton DJ, Sadeyen J-R, Chang P, Sealy JE.,d, Bryant JE, Martin SR., Shelton H, McCauley JW, Barclay WS, Iqbal M (2017) Variability in H9N2 haemagglutinin receptor binding preference and pH of fusion. Emerging Microbes & Infections 6, e11 2. Peacock T, Reddy K, James J, Adamiak B, Barclay W, Shelton H, Iqbal M (2016). Antigenic mapping of an H9N2 avian influenza virus reveals two discrete antigenic sites and a novel mechanism of immune escape. Scientific Reports 5: 18745. doi: 10.1038/srep18745. 3. Thuy DM, Peacock TP., Bich VTN, . Iqbal M, Juliet E. Bryant (2016). Prevalence and diversity of H9N2 avian influenza in chickens of Northern Vietnam, 2014. Infection, Genetics and Evolution 44: 530-540
Start Year 2014
 
Description Development of novel diagnostic tools and vaccines 
Organisation National Agricultural Research Centre
Country Pakistan 
Sector Public 
PI Contribution The outcomes of research led to incite new collaborations with following partners in UK, Vietnam and Pakistan. Together with partners we apply for the collaborative research grant to BBSRC entitled "Combating avian influenza through systematic analysis of antigenic drift, genetic variation, and development of novel diagnostic tools and vaccines". That led to further improvement avian influenza virus vaccines and diagnostics and a number of research publication.
Collaborator Contribution The partners are evaluating the potency and efficacy of vaccines in countries where the disease is enzootic in poultry.
Impact 1. Peacock TP, Benton DJ, Sadeyen J-R, Chang P, Sealy JE.,d, Bryant JE, Martin SR., Shelton H, McCauley JW, Barclay WS, Iqbal M (2017) Variability in H9N2 haemagglutinin receptor binding preference and pH of fusion. Emerging Microbes & Infections 6, e11 2. Peacock T, Reddy K, James J, Adamiak B, Barclay W, Shelton H, Iqbal M (2016). Antigenic mapping of an H9N2 avian influenza virus reveals two discrete antigenic sites and a novel mechanism of immune escape. Scientific Reports 5: 18745. doi: 10.1038/srep18745. 3. Thuy DM, Peacock TP., Bich VTN, . Iqbal M, Juliet E. Bryant (2016). Prevalence and diversity of H9N2 avian influenza in chickens of Northern Vietnam, 2014. Infection, Genetics and Evolution 44: 530-540
Start Year 2014
 
Description Development of novel diagnostic tools and vaccines 
Organisation University of Oxford
Department Oxford University Clinical Research Unit Vietnam (OUCRU)
Country Viet Nam 
Sector Academic/University 
PI Contribution The outcomes of research led to incite new collaborations with following partners in UK, Vietnam and Pakistan. Together with partners we apply for the collaborative research grant to BBSRC entitled "Combating avian influenza through systematic analysis of antigenic drift, genetic variation, and development of novel diagnostic tools and vaccines". That led to further improvement avian influenza virus vaccines and diagnostics and a number of research publication.
Collaborator Contribution The partners are evaluating the potency and efficacy of vaccines in countries where the disease is enzootic in poultry.
Impact 1. Peacock TP, Benton DJ, Sadeyen J-R, Chang P, Sealy JE.,d, Bryant JE, Martin SR., Shelton H, McCauley JW, Barclay WS, Iqbal M (2017) Variability in H9N2 haemagglutinin receptor binding preference and pH of fusion. Emerging Microbes & Infections 6, e11 2. Peacock T, Reddy K, James J, Adamiak B, Barclay W, Shelton H, Iqbal M (2016). Antigenic mapping of an H9N2 avian influenza virus reveals two discrete antigenic sites and a novel mechanism of immune escape. Scientific Reports 5: 18745. doi: 10.1038/srep18745. 3. Thuy DM, Peacock TP., Bich VTN, . Iqbal M, Juliet E. Bryant (2016). Prevalence and diversity of H9N2 avian influenza in chickens of Northern Vietnam, 2014. Infection, Genetics and Evolution 44: 530-540
Start Year 2014
 
Description Development of novel diagnostic tools and vaccines 
Organisation University of Veterinary & Animal Sciences
Country Pakistan 
Sector Academic/University 
PI Contribution The outcomes of research led to incite new collaborations with following partners in UK, Vietnam and Pakistan. Together with partners we apply for the collaborative research grant to BBSRC entitled "Combating avian influenza through systematic analysis of antigenic drift, genetic variation, and development of novel diagnostic tools and vaccines". That led to further improvement avian influenza virus vaccines and diagnostics and a number of research publication.
Collaborator Contribution The partners are evaluating the potency and efficacy of vaccines in countries where the disease is enzootic in poultry.
Impact 1. Peacock TP, Benton DJ, Sadeyen J-R, Chang P, Sealy JE.,d, Bryant JE, Martin SR., Shelton H, McCauley JW, Barclay WS, Iqbal M (2017) Variability in H9N2 haemagglutinin receptor binding preference and pH of fusion. Emerging Microbes & Infections 6, e11 2. Peacock T, Reddy K, James J, Adamiak B, Barclay W, Shelton H, Iqbal M (2016). Antigenic mapping of an H9N2 avian influenza virus reveals two discrete antigenic sites and a novel mechanism of immune escape. Scientific Reports 5: 18745. doi: 10.1038/srep18745. 3. Thuy DM, Peacock TP., Bich VTN, . Iqbal M, Juliet E. Bryant (2016). Prevalence and diversity of H9N2 avian influenza in chickens of Northern Vietnam, 2014. Infection, Genetics and Evolution 44: 530-540
Start Year 2014
 
Description Investigating antigenic determinants inducing stronger and broader cross-protective immunity among H5 avian influenza viruses 
Organisation Royal Veterinary College (RVC)
Department Veterinary Basic Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution The overarching aims of the proposed research are to improve controls against H5 subtype of avian influenza viruses infecting poultry by investigating underlying mechanisms that define how vaccines renders effectiveness and develop novel approaches enhancing the effectiveness of H5 avian influenza vaccines. We recently generated a panel of monoclonal antibodies (mAbs) that recognise a variety of different clades of H5 viruses. Propagation of AIV in eggs or cultured cells together with mAbs drives virus to escape from mAbs neutralisation activity. These classical virus neutralization assays (VN) followed by HA gene sequence analysis allowed us to defined the role of amino acid substitutions that are associated with evasion of antibody neutralization through emergence of antigenic variants and failure of vaccine efficacy.
Collaborator Contribution provided intellectual input for achieving prescribed objectives of this work.
Impact Talk entitled "Molecular determinants for antigenicity and vaccine efficacy of avian influenza viruses" was presented at Newton Agham Researcher Links Workshop " Novel Vaccines and Diagnostic Technologies against Emerging and re-emerging Veterinary Pathogens" at Rizal Park Hotel, Manila, Philippines, 4-7 February 2019.
Start Year 2019
 
Description Investigating antigenic determinants inducing stronger and broader cross-protective immunity among H5 avian influenza viruses. 
Organisation Royal Veterinary College (RVC)
Country United Kingdom 
Sector Academic/University 
PI Contribution We developed research programme to characterise diversity of antigenic epitopes induce protective immunity in chickens against H5 subtypes of avian influenza viruses.
Collaborator Contribution Collaborating partner Dr Nicola Lewis at Royal Veterinary College provide advise to on cartography programme to visualize the antigenic similarity or difference among different strains of influenza viruses.
Impact The work under this collaborative determined the antigenic differences among different clades of H5 avian influenza viruses circulating in birds. This project is multi-disciplinary. our laboratory mainly work on virology and immunology part of the project and we seek help on computer modeling part from the collaborating partner Dr Nicola Lewis.
Start Year 2019
 
Description Molecular epidemiology of H9N2 avian influenza viruses in Vietnam and Pakistan. 
Organisation Royal Veterinary College (RVC)
Country United Kingdom 
Sector Academic/University 
PI Contribution Exchange of technical ideas, reagents and samples.
Collaborator Contribution Provision of field samples and data on avian influenza infection in poultry. This diseases is endemic in poultry in Pakistan.
Impact (1) Increased receptor binding avidity of H9N2 avian influenza viruses is associated with escape from antibody based immunity and enhanced zoonotic potential. presented by Joshua Sealy at GARAD and ZELS conferences in Haneoi, Vietnam from 17-27 January 2018.
Start Year 2008
 
Description Molecular epidemiology of H9N2 avian influenza viruses in Vietnam and Pakistan. 
Organisation University of Veterinary & Animal Sciences
Department Department of Microbiology
Country Pakistan 
Sector Academic/University 
PI Contribution Exchange of technical ideas, reagents and samples.
Collaborator Contribution Provision of field samples and data on avian influenza infection in poultry. This diseases is endemic in poultry in Pakistan.
Impact (1) Increased receptor binding avidity of H9N2 avian influenza viruses is associated with escape from antibody based immunity and enhanced zoonotic potential. presented by Joshua Sealy at GARAD and ZELS conferences in Haneoi, Vietnam from 17-27 January 2018.
Start Year 2008
 
Description Morphological differences of Influenza A viruses 
Organisation University of Edinburgh
Department The Roslin Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Exchange of research methods and reagents
Collaborator Contribution (1) Exchange of reagents and Research methods.(2) training of PhD students and Postdoctoral Scientists (3) use of research facilities
Impact Research output were presented at Avian Influenza A virus budding morphology: spherical or filamentous? presented at The European Scientific Working group on Influenza (ESWI) Riga, Latvia. 10 to 13 September 2017 (2) .Budding morphology of avian influenza A viruses. Microbiology Society, annual Conference 2017, 306 April, EICC, Edinburggh, UK
Start Year 2016
 
Description The GCRF One Health Poultry Hub 
Organisation Royal Veterinary College (RVC)
Country United Kingdom 
Sector Academic/University 
PI Contribution The focus of the research is to achieve sustainable global intensification of poultry meat and egg production whilst reducing risks to human and animal health and welfare. We are undertaking research to investigate the diversity of avian influenza viruses prevalent in poultry and wild birds in south east Asia.
Collaborator Contribution Royal Veterinary College, London is leading this GCRF One Health Poultry Hub. The project will address the need to meet rising demand for poultry meat and eggs in developing countries, while minimising risk to international public health. Population growth is driving global demand for poultry, meat and egg production; this unfortunately creates conditions in which animal diseases can spread to humans ('zoonoses'). These include bacterial food poisoning and strains with avian influenza with epidemic or pandemic potential. The GCRF One Health Poultry Hub will adopt a 'One Health' approach to the issue of combatting animal-to-human diseases by bringing together a team of laboratory, clinical, veterinary and social scientists. This team will test and evaluate novel interventions. The need for safe poultry production is most urgent in South and South East Asia, so the RVC and its partners will then use their local networks in these regions to put its positive research to immediate use.
Impact Development of international interdisciplinary partnership of 55 investigators from 13 countries to address the emerging global challenges of food security and public health associated with intensification of poultry production.
Start Year 2018
 
Description The Pirbright "Livestock Antibody Hub" funded by Bill & Melinda Gates Foundation 
Organisation The Pirbright Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Me and my team established collaboration in the "Livestock Antibody Hub" funded ($5.5 million) by the from Bill & Melinda Gates Foundation. Focus of our partnership is to develop techniques and capacity to analyse immune cells (B cells) of cattle, poultry and pigs that produce virus neutralizing antibodies. This research will support rational development of next generation of vaccines and to explore antibody-based passive immunization approaches for treatment and prophylaxis of infectious viral diseases affecting livestock and humans. Our initial focus is to target major animal viral pathogens that cause severe losses within Low and Middle-Income Countries (LMIC) animal production systems including avian influenza virus (AIV), Newcastle disease virus (NDV), infectious bursal disease virus (IBDV), infectious bronchitis virus (IBV) and foot-and-mouth disease virus (FMDV).
Collaborator Contribution This is a collaborative project and partners are providing help in provision of reagents and techniques for analysis of diversity of B cells repertoire that produce infleunza virus-specific antibodies, single cell sequencing and bioinformatic analysis. This project will further strengthen our on-going research collaborations with many research groups in academia as well as with animal health industry (Zoetis, Boehringer Ingelheim Animal Health, Merck, CEVA, Jovac, YeBio, ILRI, Galvmed, The Roslin Institute, HuMabs, AbCellera and Distributed Bio) to take the research outputs from laboratory to the field. The outputs of research will be improved vaccines and diagnostics enabling to reduce the impact of infectious diseases on farm animals, which offer substantial direct and indirect economic, public health, environmental and social benefits to the UK and rest of the world.
Impact Development of passive immunization approaches against avian influenza viruses affecting poultry (project incited in January 2020).
Start Year 2020
 
Description The role of segment 3 in H9N2 avian influenza virus pathogenicity 
Organisation University of Edinburgh
Department The Roslin Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a Joint studentship project funded by The Pirbright Institute and The Roslin Institute. We identiifed molecular markers that are responsible for increase in virus pathogenicity and transmission.
Collaborator Contribution The Roslin Institute contributed both intellectually and by proving research training, samples and regents to achieve the prescribed objectives this project.
Impact 1. Oral Presentation Title: Identification of segment 3 sequence polymorphisms which alter shut off activity and pathogenicity of H9N2 avian influenza viruses in vivo. Anabel Clements, Saira Hussain, Holly Shelton, Paul Digard and Munir Iqbal. Global Alliance for Research Into Avian Diseases (GARAD). January 17th to 19th 2018. Fortuna Hotel, Lang Ha Street, Hanoi, VietNam 2. Poster title: What is the role of H9N2 avian influenza virus PA-X within an avian model?. Anabel Clements, Saira Hussain, Holly Shelton, Paul Digard & Munir Iqbal. UK- China CERAD (Centre of Excellence for Research on Avian Diseases), 3rd Symposium Recent Advances in Avian Disease Research. August 31st - 1st September 2017. The Harbour Hotel, Alexandra Terrace, Guildford, Surrey, UK. 3. Poster title: What is the role of H9N2 avian influenza virus PA-X within an avian model?. Anabel Clements, Saira Hussain, Holly Shelton, Paul Digard & Munir Iqbal. Microbiology Society Annual Conference. April 3rd-6th 2017. Edinburgh International Conference Centre (EICC), Edinburgh, UK. 4. Oral Presentation title: Identification of sequence polymorphisms in segment 3 of H9N2 avian influenza viruses that affect PA-X activity. Anabel Clements, Saira Hussain, Holly Shelton, Paul Digard & Munir Iqbal. Focused Meeting 2016: Molecular Biology and Pathogenesis of Avian Viruses. September 27th-29th 2016. Charles Darwin House, London, UK. 5. Oral Presentation title: The role of segment 3 in H9N2 avian influenza virus pathogenicity. Anabel Clements, Saira Hussain, Holly Shelton, Munir Iqbal & Paul Digard. UK -Taiwan BBSRC Partnering Award workshop: Improving Control of influenza viruses. 26th-27th April 2016. Taipei, Taiwan. 6. Oral Presentation title: Identification of sequence polymorphisms in segment 3 of H9N2 avian influenza viruses that affect PA-X activity. Anabel Clements, Saira Hussain, Holly Shelton, Munir Iqbal & Paul Digard. Microbiology Society Annual Conference 2016; virus Workshop: Negative strand RNA Viruses. 21st-24th March 2016. Arena and Convention Centre, Liverpool, UK. 7. Poster title: The role of segment 3 in H9N2 influenza virus pathogenicity. Anabel Clements, Saira Hussain, Holly Shelton, Munir Iqbal & Paul Digard. 7th Orthomyxovirus research conference. 16th-18th September 2015. Ecole Nationale Veterinaire de Toulouse, Toulouse, France. 8. Poster title: The role of segment 3 in H9N2 influenza virus pathogenicity. Anabel Clements, Saira Hussain, Holly Shelton, Munir Iqbal & Paul Digard. Edinburgh Infectious Diseases Annual Symposium. 20th May 2015. Royal College of Physicians, Edinburgh, UK.
Start Year 2014
 
Description Understanding antigenic diversity, zoonotic potential and immunological prevention of avian influenza viruses affecting poultry 
Organisation Beijing Academy of Agriculture and Forestry Sciences
Country China 
Sector Academic/University 
PI Contribution Undertake joint research work to investigate to identify the molecular determinants that are critical for enhancing potency and efficacy of vaccines, as well as those that are associated with heightened zoonotic risk.
Collaborator Contribution Provision of samples, reagents and research facilities
Impact Published joint paper (1)ian Xu, Xixi Zhang, Shuanghai Zhou, Junjun Shen,Dawei Yang, Jing Wu, Xiaoyang Li, Meiling Li, Xiufen Huang, Joshua E. Sealy, Munir Iqbal&Yongqing Li (2017). A DNA aptamer efficiently inhibits the infectivity of Bovine herpesvirus 1 by blocking viral entry. Scientific Reports. 7: 11796. doi:10.1038/s41598-017-10070-1. (2) Jian Xu, Jing Wu, Houjun He, Junjun Shena, Dawei Yang, Xixi Zhang, Xiaoyang Li, Meiling Li, Xiufen Huang, Joshua Sealy, Munir Iqbal & Yongqing Li (2017). Bovine single chain Fv antibody inhibits bovine herpesvirus-1 infectivity by targeting viral glycoprotein D. Applied Microbiology and Biotechnology. https://doi.org/10.1007/s00253-017-8566-0. (2)
Start Year 2017
 
Description Understanding antigenic diversity, zoonotic potential and immunological prevention of avian influenza viruses affecting poultry 
Organisation China Agricultural University (CAU)
Department College of Veterinary Medicine
Country China 
Sector Academic/University 
PI Contribution Undertake joint research work to investigate to identify the molecular determinants that are critical for enhancing potency and efficacy of vaccines, as well as those that are associated with heightened zoonotic risk.
Collaborator Contribution Provision of samples, reagents and research facilities
Impact Published joint paper (1)ian Xu, Xixi Zhang, Shuanghai Zhou, Junjun Shen,Dawei Yang, Jing Wu, Xiaoyang Li, Meiling Li, Xiufen Huang, Joshua E. Sealy, Munir Iqbal&Yongqing Li (2017). A DNA aptamer efficiently inhibits the infectivity of Bovine herpesvirus 1 by blocking viral entry. Scientific Reports. 7: 11796. doi:10.1038/s41598-017-10070-1. (2) Jian Xu, Jing Wu, Houjun He, Junjun Shena, Dawei Yang, Xixi Zhang, Xiaoyang Li, Meiling Li, Xiufen Huang, Joshua Sealy, Munir Iqbal & Yongqing Li (2017). Bovine single chain Fv antibody inhibits bovine herpesvirus-1 infectivity by targeting viral glycoprotein D. Applied Microbiology and Biotechnology. https://doi.org/10.1007/s00253-017-8566-0. (2)
Start Year 2017
 
Description Understanding antigenic diversity, zoonotic potential and immunological prevention of avian influenza viruses affecting poultry 
Organisation Chinese Center for Disease Control and Prevention (China CDC)
Country China 
Sector Public 
PI Contribution Undertake joint research work to investigate to identify the molecular determinants that are critical for enhancing potency and efficacy of vaccines, as well as those that are associated with heightened zoonotic risk.
Collaborator Contribution Provision of samples, reagents and research facilities
Impact Published joint paper (1)ian Xu, Xixi Zhang, Shuanghai Zhou, Junjun Shen,Dawei Yang, Jing Wu, Xiaoyang Li, Meiling Li, Xiufen Huang, Joshua E. Sealy, Munir Iqbal&Yongqing Li (2017). A DNA aptamer efficiently inhibits the infectivity of Bovine herpesvirus 1 by blocking viral entry. Scientific Reports. 7: 11796. doi:10.1038/s41598-017-10070-1. (2) Jian Xu, Jing Wu, Houjun He, Junjun Shena, Dawei Yang, Xixi Zhang, Xiaoyang Li, Meiling Li, Xiufen Huang, Joshua Sealy, Munir Iqbal & Yongqing Li (2017). Bovine single chain Fv antibody inhibits bovine herpesvirus-1 infectivity by targeting viral glycoprotein D. Applied Microbiology and Biotechnology. https://doi.org/10.1007/s00253-017-8566-0. (2)
Start Year 2017
 
Description Understanding antigenic diversity, zoonotic potential and immunological prevention of avian influenza viruses affecting poultry 
Organisation Francis Crick Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Undertake joint research work to investigate to identify the molecular determinants that are critical for enhancing potency and efficacy of vaccines, as well as those that are associated with heightened zoonotic risk.
Collaborator Contribution Provision of samples, reagents and research facilities
Impact Published joint paper (1)ian Xu, Xixi Zhang, Shuanghai Zhou, Junjun Shen,Dawei Yang, Jing Wu, Xiaoyang Li, Meiling Li, Xiufen Huang, Joshua E. Sealy, Munir Iqbal&Yongqing Li (2017). A DNA aptamer efficiently inhibits the infectivity of Bovine herpesvirus 1 by blocking viral entry. Scientific Reports. 7: 11796. doi:10.1038/s41598-017-10070-1. (2) Jian Xu, Jing Wu, Houjun He, Junjun Shena, Dawei Yang, Xixi Zhang, Xiaoyang Li, Meiling Li, Xiufen Huang, Joshua Sealy, Munir Iqbal & Yongqing Li (2017). Bovine single chain Fv antibody inhibits bovine herpesvirus-1 infectivity by targeting viral glycoprotein D. Applied Microbiology and Biotechnology. https://doi.org/10.1007/s00253-017-8566-0. (2)
Start Year 2017
 
Description Understanding antigenic diversity, zoonotic potential and immunological prevention of avian influenza viruses affecting poultry 
Organisation University of Glasgow
Department Institute of Biodiversity, Animal Health and Comparative Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Undertake joint research work to investigate to identify the molecular determinants that are critical for enhancing potency and efficacy of vaccines, as well as those that are associated with heightened zoonotic risk.
Collaborator Contribution Provision of samples, reagents and research facilities
Impact Published joint paper (1)ian Xu, Xixi Zhang, Shuanghai Zhou, Junjun Shen,Dawei Yang, Jing Wu, Xiaoyang Li, Meiling Li, Xiufen Huang, Joshua E. Sealy, Munir Iqbal&Yongqing Li (2017). A DNA aptamer efficiently inhibits the infectivity of Bovine herpesvirus 1 by blocking viral entry. Scientific Reports. 7: 11796. doi:10.1038/s41598-017-10070-1. (2) Jian Xu, Jing Wu, Houjun He, Junjun Shena, Dawei Yang, Xixi Zhang, Xiaoyang Li, Meiling Li, Xiufen Huang, Joshua Sealy, Munir Iqbal & Yongqing Li (2017). Bovine single chain Fv antibody inhibits bovine herpesvirus-1 infectivity by targeting viral glycoprotein D. Applied Microbiology and Biotechnology. https://doi.org/10.1007/s00253-017-8566-0. (2)
Start Year 2017
 
Description Understanding diversity of avian influenza viruses and improvement disease control in poultry and humans 
Organisation Agricultural Research Centre
Department Veterinary Serum and Vaccine Research Institute
Country Egypt 
Sector Public 
PI Contribution This project helped my research group to establish research collboration between the Pirbright Institute and the scientists at the collaborating laboratories listed above and an excellent opportunity for building a joint "ONE HEALTH" platfor. I am sharing knowledge, reagents and techniques to improve efficacious vaccines and diagnostic tools against avian influenza viruses. The easy availability of better control tools against avian influenza viruses will aid in the reduction of poultry production losses and thus be important for global food security and improved animal welfare whilst also reducing zoonotic transmission to humans.
Collaborator Contribution Each collaborating institute and team member has specific expertise and facilities in areas relevant to this research programme. Collaborators in different institutions have extensive experience collecting field samples and implementing vaccination and large scale surveillance programmes. Each partner institutions have unique experience in monitoring the endemic prevalence of many animal diseases including avian influenza in both domestic and wild birds from which UK is under constant threat. The partners are sharing knowledge, expertise and facilities to investigate fundamental biology of influenza viruses and predict their epidemiological relevance, to assess potential risks and to devise appropriate intervention strategies. The knowledge, reagents and field samples will be available through this partnership. which will be essential for development of informed control policies and tools(vaccines and diagnostics) that may contribute to reducing the ever increasing threat from endemic, emerging and re-emerging influenza virus variants posing risk to animals and humans. Also, All researchers involved will benefit through ongoing professional development and advanced training in new technologies and new systems-level approaches to disease management. Exchange visits of researchers from collaborating laboratories to undertake training in a number of disciplines including disease surveillance, molecular virology, epidemiology, immunology, vaccinology and diagnostics will have a tangible impact on capacity building and training of next generation researchers in control of infectious animal and zoonotic diseases.
Impact The ultimate aims of this collaboration are to reduce the impact of influenza virus on poultry production and reduce their zoonotic transmission to humans. The collaboration will improve resources and capacity for disease control systems. Achieving these specific goals will prove a step-change in AIV disease management and increase in poultry productivity directly drives economic prosperity of farmers and allied communities. The will directly impact on socio-economic well-being of partner countries.
Start Year 2017
 
Description Understanding diversity of avian influenza viruses and improvement disease control in poultry and humans 
Organisation Francis Crick Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution This project helped my research group to establish research collboration between the Pirbright Institute and the scientists at the collaborating laboratories listed above and an excellent opportunity for building a joint "ONE HEALTH" platfor. I am sharing knowledge, reagents and techniques to improve efficacious vaccines and diagnostic tools against avian influenza viruses. The easy availability of better control tools against avian influenza viruses will aid in the reduction of poultry production losses and thus be important for global food security and improved animal welfare whilst also reducing zoonotic transmission to humans.
Collaborator Contribution Each collaborating institute and team member has specific expertise and facilities in areas relevant to this research programme. Collaborators in different institutions have extensive experience collecting field samples and implementing vaccination and large scale surveillance programmes. Each partner institutions have unique experience in monitoring the endemic prevalence of many animal diseases including avian influenza in both domestic and wild birds from which UK is under constant threat. The partners are sharing knowledge, expertise and facilities to investigate fundamental biology of influenza viruses and predict their epidemiological relevance, to assess potential risks and to devise appropriate intervention strategies. The knowledge, reagents and field samples will be available through this partnership. which will be essential for development of informed control policies and tools(vaccines and diagnostics) that may contribute to reducing the ever increasing threat from endemic, emerging and re-emerging influenza virus variants posing risk to animals and humans. Also, All researchers involved will benefit through ongoing professional development and advanced training in new technologies and new systems-level approaches to disease management. Exchange visits of researchers from collaborating laboratories to undertake training in a number of disciplines including disease surveillance, molecular virology, epidemiology, immunology, vaccinology and diagnostics will have a tangible impact on capacity building and training of next generation researchers in control of infectious animal and zoonotic diseases.
Impact The ultimate aims of this collaboration are to reduce the impact of influenza virus on poultry production and reduce their zoonotic transmission to humans. The collaboration will improve resources and capacity for disease control systems. Achieving these specific goals will prove a step-change in AIV disease management and increase in poultry productivity directly drives economic prosperity of farmers and allied communities. The will directly impact on socio-economic well-being of partner countries.
Start Year 2017
 
Description Understanding diversity of avian influenza viruses and improvement disease control in poultry and humans 
Organisation Imperial College London
Department MSk Lab
Country United Kingdom 
Sector Academic/University 
PI Contribution This project helped my research group to establish research collboration between the Pirbright Institute and the scientists at the collaborating laboratories listed above and an excellent opportunity for building a joint "ONE HEALTH" platfor. I am sharing knowledge, reagents and techniques to improve efficacious vaccines and diagnostic tools against avian influenza viruses. The easy availability of better control tools against avian influenza viruses will aid in the reduction of poultry production losses and thus be important for global food security and improved animal welfare whilst also reducing zoonotic transmission to humans.
Collaborator Contribution Each collaborating institute and team member has specific expertise and facilities in areas relevant to this research programme. Collaborators in different institutions have extensive experience collecting field samples and implementing vaccination and large scale surveillance programmes. Each partner institutions have unique experience in monitoring the endemic prevalence of many animal diseases including avian influenza in both domestic and wild birds from which UK is under constant threat. The partners are sharing knowledge, expertise and facilities to investigate fundamental biology of influenza viruses and predict their epidemiological relevance, to assess potential risks and to devise appropriate intervention strategies. The knowledge, reagents and field samples will be available through this partnership. which will be essential for development of informed control policies and tools(vaccines and diagnostics) that may contribute to reducing the ever increasing threat from endemic, emerging and re-emerging influenza virus variants posing risk to animals and humans. Also, All researchers involved will benefit through ongoing professional development and advanced training in new technologies and new systems-level approaches to disease management. Exchange visits of researchers from collaborating laboratories to undertake training in a number of disciplines including disease surveillance, molecular virology, epidemiology, immunology, vaccinology and diagnostics will have a tangible impact on capacity building and training of next generation researchers in control of infectious animal and zoonotic diseases.
Impact The ultimate aims of this collaboration are to reduce the impact of influenza virus on poultry production and reduce their zoonotic transmission to humans. The collaboration will improve resources and capacity for disease control systems. Achieving these specific goals will prove a step-change in AIV disease management and increase in poultry productivity directly drives economic prosperity of farmers and allied communities. The will directly impact on socio-economic well-being of partner countries.
Start Year 2017
 
Description Understanding diversity of avian influenza viruses and improvement disease control in poultry and humans 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution This project helped my research group to establish research collboration between the Pirbright Institute and the scientists at the collaborating laboratories listed above and an excellent opportunity for building a joint "ONE HEALTH" platfor. I am sharing knowledge, reagents and techniques to improve efficacious vaccines and diagnostic tools against avian influenza viruses. The easy availability of better control tools against avian influenza viruses will aid in the reduction of poultry production losses and thus be important for global food security and improved animal welfare whilst also reducing zoonotic transmission to humans.
Collaborator Contribution Each collaborating institute and team member has specific expertise and facilities in areas relevant to this research programme. Collaborators in different institutions have extensive experience collecting field samples and implementing vaccination and large scale surveillance programmes. Each partner institutions have unique experience in monitoring the endemic prevalence of many animal diseases including avian influenza in both domestic and wild birds from which UK is under constant threat. The partners are sharing knowledge, expertise and facilities to investigate fundamental biology of influenza viruses and predict their epidemiological relevance, to assess potential risks and to devise appropriate intervention strategies. The knowledge, reagents and field samples will be available through this partnership. which will be essential for development of informed control policies and tools(vaccines and diagnostics) that may contribute to reducing the ever increasing threat from endemic, emerging and re-emerging influenza virus variants posing risk to animals and humans. Also, All researchers involved will benefit through ongoing professional development and advanced training in new technologies and new systems-level approaches to disease management. Exchange visits of researchers from collaborating laboratories to undertake training in a number of disciplines including disease surveillance, molecular virology, epidemiology, immunology, vaccinology and diagnostics will have a tangible impact on capacity building and training of next generation researchers in control of infectious animal and zoonotic diseases.
Impact The ultimate aims of this collaboration are to reduce the impact of influenza virus on poultry production and reduce their zoonotic transmission to humans. The collaboration will improve resources and capacity for disease control systems. Achieving these specific goals will prove a step-change in AIV disease management and increase in poultry productivity directly drives economic prosperity of farmers and allied communities. The will directly impact on socio-economic well-being of partner countries.
Start Year 2017
 
Description Understanding diversity of avian influenza viruses and improvement disease control in poultry and humans 
Organisation Suez Canal University
Country Egypt 
Sector Academic/University 
PI Contribution This project helped my research group to establish research collboration between the Pirbright Institute and the scientists at the collaborating laboratories listed above and an excellent opportunity for building a joint "ONE HEALTH" platfor. I am sharing knowledge, reagents and techniques to improve efficacious vaccines and diagnostic tools against avian influenza viruses. The easy availability of better control tools against avian influenza viruses will aid in the reduction of poultry production losses and thus be important for global food security and improved animal welfare whilst also reducing zoonotic transmission to humans.
Collaborator Contribution Each collaborating institute and team member has specific expertise and facilities in areas relevant to this research programme. Collaborators in different institutions have extensive experience collecting field samples and implementing vaccination and large scale surveillance programmes. Each partner institutions have unique experience in monitoring the endemic prevalence of many animal diseases including avian influenza in both domestic and wild birds from which UK is under constant threat. The partners are sharing knowledge, expertise and facilities to investigate fundamental biology of influenza viruses and predict their epidemiological relevance, to assess potential risks and to devise appropriate intervention strategies. The knowledge, reagents and field samples will be available through this partnership. which will be essential for development of informed control policies and tools(vaccines and diagnostics) that may contribute to reducing the ever increasing threat from endemic, emerging and re-emerging influenza virus variants posing risk to animals and humans. Also, All researchers involved will benefit through ongoing professional development and advanced training in new technologies and new systems-level approaches to disease management. Exchange visits of researchers from collaborating laboratories to undertake training in a number of disciplines including disease surveillance, molecular virology, epidemiology, immunology, vaccinology and diagnostics will have a tangible impact on capacity building and training of next generation researchers in control of infectious animal and zoonotic diseases.
Impact The ultimate aims of this collaboration are to reduce the impact of influenza virus on poultry production and reduce their zoonotic transmission to humans. The collaboration will improve resources and capacity for disease control systems. Achieving these specific goals will prove a step-change in AIV disease management and increase in poultry productivity directly drives economic prosperity of farmers and allied communities. The will directly impact on socio-economic well-being of partner countries.
Start Year 2017
 
Description Understanding diversity of avian influenza viruses and improvement disease control in poultry and humans 
Organisation University of Tokyo
Department International Research Center for Infectious Diseases
Country Japan 
Sector Hospitals 
PI Contribution This project helped my research group to establish research collboration between the Pirbright Institute and the scientists at the collaborating laboratories listed above and an excellent opportunity for building a joint "ONE HEALTH" platfor. I am sharing knowledge, reagents and techniques to improve efficacious vaccines and diagnostic tools against avian influenza viruses. The easy availability of better control tools against avian influenza viruses will aid in the reduction of poultry production losses and thus be important for global food security and improved animal welfare whilst also reducing zoonotic transmission to humans.
Collaborator Contribution Each collaborating institute and team member has specific expertise and facilities in areas relevant to this research programme. Collaborators in different institutions have extensive experience collecting field samples and implementing vaccination and large scale surveillance programmes. Each partner institutions have unique experience in monitoring the endemic prevalence of many animal diseases including avian influenza in both domestic and wild birds from which UK is under constant threat. The partners are sharing knowledge, expertise and facilities to investigate fundamental biology of influenza viruses and predict their epidemiological relevance, to assess potential risks and to devise appropriate intervention strategies. The knowledge, reagents and field samples will be available through this partnership. which will be essential for development of informed control policies and tools(vaccines and diagnostics) that may contribute to reducing the ever increasing threat from endemic, emerging and re-emerging influenza virus variants posing risk to animals and humans. Also, All researchers involved will benefit through ongoing professional development and advanced training in new technologies and new systems-level approaches to disease management. Exchange visits of researchers from collaborating laboratories to undertake training in a number of disciplines including disease surveillance, molecular virology, epidemiology, immunology, vaccinology and diagnostics will have a tangible impact on capacity building and training of next generation researchers in control of infectious animal and zoonotic diseases.
Impact The ultimate aims of this collaboration are to reduce the impact of influenza virus on poultry production and reduce their zoonotic transmission to humans. The collaboration will improve resources and capacity for disease control systems. Achieving these specific goals will prove a step-change in AIV disease management and increase in poultry productivity directly drives economic prosperity of farmers and allied communities. The will directly impact on socio-economic well-being of partner countries.
Start Year 2017
 
Description Understanding diversity of avian influenza viruses and improvement disease control in poultry and humans 
Organisation Zagazig University
Country Egypt 
Sector Academic/University 
PI Contribution This project helped my research group to establish research collboration between the Pirbright Institute and the scientists at the collaborating laboratories listed above and an excellent opportunity for building a joint "ONE HEALTH" platfor. I am sharing knowledge, reagents and techniques to improve efficacious vaccines and diagnostic tools against avian influenza viruses. The easy availability of better control tools against avian influenza viruses will aid in the reduction of poultry production losses and thus be important for global food security and improved animal welfare whilst also reducing zoonotic transmission to humans.
Collaborator Contribution Each collaborating institute and team member has specific expertise and facilities in areas relevant to this research programme. Collaborators in different institutions have extensive experience collecting field samples and implementing vaccination and large scale surveillance programmes. Each partner institutions have unique experience in monitoring the endemic prevalence of many animal diseases including avian influenza in both domestic and wild birds from which UK is under constant threat. The partners are sharing knowledge, expertise and facilities to investigate fundamental biology of influenza viruses and predict their epidemiological relevance, to assess potential risks and to devise appropriate intervention strategies. The knowledge, reagents and field samples will be available through this partnership. which will be essential for development of informed control policies and tools(vaccines and diagnostics) that may contribute to reducing the ever increasing threat from endemic, emerging and re-emerging influenza virus variants posing risk to animals and humans. Also, All researchers involved will benefit through ongoing professional development and advanced training in new technologies and new systems-level approaches to disease management. Exchange visits of researchers from collaborating laboratories to undertake training in a number of disciplines including disease surveillance, molecular virology, epidemiology, immunology, vaccinology and diagnostics will have a tangible impact on capacity building and training of next generation researchers in control of infectious animal and zoonotic diseases.
Impact The ultimate aims of this collaboration are to reduce the impact of influenza virus on poultry production and reduce their zoonotic transmission to humans. The collaboration will improve resources and capacity for disease control systems. Achieving these specific goals will prove a step-change in AIV disease management and increase in poultry productivity directly drives economic prosperity of farmers and allied communities. The will directly impact on socio-economic well-being of partner countries.
Start Year 2017
 
Description Talk Presented at 2nd International Congress of Veterinary Microbiology, 16th -19th October 2018. Sherwood Breezes Resort-Lara, Antalya, Turkey. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Conference discussed improving prevention and control of viral diseases of poultry.
Year(s) Of Engagement Activity 2018
 
Description "Challenges for Poultry Industry". Organised by Fakieh Poultry at the Ritz-Carlton Hotel in Jeddah, Saudi Arabia, 2nd -3rd December 2018, 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Conference discussed prevention and control of infectious diseases affecting poultry production.
Year(s) Of Engagement Activity 2018
 
Description "Interactive session with poultry stakeholders". Title: Overview of Avian Influenza group Research at The Pirbright Institute. Presented at University of Veterinary and Animal Sciences (UVAS) Lahore, Pakistan, 3rd August 2018. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The workshop discussed the economic impacts and prevention strategies against avian influenza viruses affecting poultry production and zoonotic infections.
Year(s) Of Engagement Activity 2018
 
Description 1. Improvement of vaccines and diagnostics for avian influenza viruses. South West Chicken Association. 28th Annual Trade Fair and Conference, 19 April 2016. Bristol, UK. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact gave the overview of scientific advances for the control of avian influenza infection and spread in poultry to farmers and representative from poultry production chain.over 200 peoples attanded South West Chicken Association. 28th Annual Trade Fair and Conference, 19 April 2016. Bristol, UK.
Year(s) Of Engagement Activity 2016
URL https://www.farminguk.com/agricultural-shows-and-events/South-West-Chicken-Association-Conference-Tr...
 
Description 2. Overview of Avian Influenza group Research at The Pirbright Institute. Presented at "Interactive session with poultry stakeholders" at University of Veterinary and Animal Sciences (UVAS) Lahore, Pakistan, 3rd August 2018. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Dissemination of research Project outcomes These include presenting research data for vaccine seed strains with emergent field avian influenza variants; The zoonotic risk posed by emerging avian influenza viruses circulating in the wild birds and poultry. Impact of virus evolution on vaccine efficacy and persistence in poultry.
Year(s) Of Engagement Activity 2018
 
Description 4. H9N2 avian influenza in chickens of northern Vietnam: prevalence, diversity, pathogenicity. Options for the Control of Infuenza IX. Chicago, Illinois, USA, 24-28 August 2016. 5. Defining the antigenic sites of H9N2 avian influenza viruses. Options for the Control of In uenza IX. Chicago, Illinois, USA, 24-28 August 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact International Influenza conference on options for the control of influenza infections in animals and humans.
Year(s) Of Engagement Activity 2016
URL http://2016.isirv.org
 
Description 5. Defining the antigenic sites of H9N2 avian influenza viruses. Options for the Control of In uenza IX. Chicago, Illinois, USA, 24-28 August 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact International conference on the control of Influenza virus infections in animals and humans..
Year(s) Of Engagement Activity 2016
URL http://2016.isirv.org
 
Description Avian Influenza H9N2 and H7N9 evolution, fitness in poultry and zoonotic potential presented by Munir Iqbal at UC DAVIS EDUCATION CONFERENCE ON ONE HEALTH FOR FOOD SAFETY, AGRICULTURE, AND ANIMAL HEALTH 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The research was discussed with academic and non-academic participants the risks of avian influenza viruses currently circulating in poultry and carry potential to cause zoonotic infections. Since avian influenzas viruses (AIVs) exist in many subtypes and co-infection of two or more different AIV subtypes in an individual bird can lead to the generation of novel reassortant viruses. The emergent reassortant viruses may carry differential phenotypic characteristics (virulence, host-transmission and host-range) compared to their parental viruses. Our studies revealed that experimental co-infection of chickens with two different subtypes of avian influenza viruses (H9N2 and H7N9) led to the emergence of novel reassortant H9N9 viruses which carry greater virulence for poultry and an increased zoonotic and pandemic potential.

Our results also provided evidence that both H9N2 and H7N9 viruses can rapidly acquire antigenic changes in vaccinated birds causing vaccine failure and cocirculation of these viruses can also rapidly lead to rapid generation of novel reassortment viruses with increased virulence and host-range posing threat to both animals and humans.

This presentation increased awareness among the audience risk posed by co-circulation of different subtypes of avian influenza viruses in poultry and wild birds and how best we can detect emerging threats and develop the disease risks and disease mitigation strategies.
Year(s) Of Engagement Activity 2021
URL https://www.wifss.ucdavis.edu/onehealthsummer21/
 
Description Avian influenza viruses can combine two techniques to evade vaccine immunity 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact A study by researchers at The Pirbright Institute reveals more clues about how avian influenza viruses can evade vaccine immunity, aiding their spread in the field. The findings are published in Emerging Microbes and Infections.

Influenza viruses are able to mutate, which can enable them to evade immunity generated by natural infection or vaccination. Influenza viruses have four main ways of duping the immune system so that they can continue to infect and spread between birds. Pirbright scientists investigated two of these to further understand how the H9N2 avian influenza virus can change its genetic makeup to overcome poultry vaccines.

One of the methods the virus can use is to alter one of its surface proteins, haemagglutinin (HA), which enables the virus to enter the cell and replicate. HA is also a common target for the immune system's antibodies, which block the virus from binding to cell receptors. By changing just one or two protein components, HA can latch on far more tightly to the cell, preventing antibodies from stopping the virus. However, this can come at a cost, as particularly strong binding can prevent effective replication.

The other method scientists investigated is how H9N2 viruses disguise themselves by adding sugar chains to the surface of their HA proteins. This can block antibodies from binding, but also has varying fitness outcomes for the influenza virus. The researchers found that the location of the sugar chain on HA could determine how effectively the virus replicated.

They also demonstrated that the two evasive techniques could either compliment or act against each other - if an influenza virus had gained mutations that enable it to bind more strongly to cells, a sugar chain in the right position could restore its ability to replicate effectively. In contrast, weakly binding influenza viruses do not benefit from HA sugar additions, which instead reduce the virus's ability to replicate.

Professor Munir Iqbal, head of the Avian Influenza Group at Pirbright said, "We can use this knowledge to develop new vaccines that will help antibodies to recognise how the flu virus can change. This will provide protection to birds even as the virus evolves. We can also use this information to understand how viruses survive in poultry despite vaccination and monitor new adaptions that may appear in the field."

This research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation (UKRI) and the British Council with support from the Newton Fund.

Article: Sealy, J. E., Peacock, T. P., Sadeyen, J. R., Chang, P., Everest, H. J., Bhat, S., Iqbal, M. (2020). Adsorptive mutation and N-linked glycosylation modulate influenza virus antigenicity and fitness. Emerging Microbes & Infections, advance online publication, 12 November 2020, doi: 10.1080/22221751.2020.1850180

[SOURCE: The Pirbright Institute]
Year(s) Of Engagement Activity 2020
URL https://www.star-idaz.net/2020/12/avian-influenza-viruses-can-combine-two-techniques-to-evade-vaccin...
 
Description Avian influenza viruses in Bangladesh, Vietnam, and Sri Lanka: investigating genotype to phenotype (antigenicity, virulence, host-range). Webinar on 28th March 2021. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented talk by Munir iqbal describing ongoing research outcomes. We identified genetic determined that modules avian influenza H5 and H9 antigenicity virulence and transmission fitness in different host species. The role of identified markers that change the virus binding to host cells and impact on virus-host interaction leading to mild or severe disease manifestation in chickens and mammalian species (humans).
Year(s) Of Engagement Activity 2021
 
Description Avian influenza: tackling large numbers of outbreaks this winter in the UK 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Nearly two years on, the COVID-19 pandemic is still dominating the news and continues to cause concern for populations across the globe. However, UK poultry and wild bird populations are currently facing their own health threat. We are not the only ones that have faced lockdowns because of spreading viruses, UK poultry and captive birds have also faced a similar situation to protect them from avian influenza. Scientists at The Pirbright Institute are working to increase understanding of how genetic changes in influenza A viruses can impact disease spread, host responses to infection and the pathology associated with the disease.

What is the avian influenza virus?
Avian influenza viruses are Influenza A viruses that circulate and transmit amongst birds. The disease is what we commonly know as 'bird flu'. Influenza A viruses can infect a range of hosts, including humans and two subtypes H1N1 and H3N2 circulate as seasonal flu each winter in the UK. Avian influenza viruses are different to those that can infect humans in that they cannot easily infect humans and must change and adapt to do so.

Aquatic birds are a natural reservoir for avian influenza viruses, these birds typically experience fewer clinical symptoms but can spread disease to domestic birds, particularly in the migratory season, between October and March. Avian influenza viruses are categorised as either highly pathogenic (HPAI) or low pathogenic (LPAI) and this categorisation is linked to the severity of disease in chickens.

HPAI has a high mortality rate which can be up to 100%, other symptoms can include swelling of the head, death of cells in the comb and wattle, red discolouration of legs and feet and diarrhoea. HPAI causes disease in more organs than just those in the respiratory or gastrointestinal tracts like LPAI, which mostly presents as respiratory symptoms such as a snick (like a sneeze), a rattle in the chest (known as rales) and discharge from the eyes and nose.

What is causing bird flu outbreaks in domestic birds now?
We are currently in the normal migratory season of wild birds. In the spring and summer months, these birds spend their time breeding and raising their young in North-eastern Asia where they mix with other bird species which enables virus transmission and mutation. Then, when they migrate for the autumn and winter months, they shed virus in their faeces along the way.

One of the migratory paths is across Northern Europe and this includes the UK. This year, in the UK, the first avian influenza outbreak was on 15 October and was discovered in captive aquatic birds. To date (17 December 2021) there have been 50 outbreaks in England, 1 in Wales and 2 in Scotland, this has resulted in over half a million birds being destroyed to control the spread of disease.

Are there more outbreaks this year compared to other years?
The number of outbreaks this year has been the most extensive ever. There have been over 50 outbreaks in the UK, compared to 26 outbreaks last year. Although it is hard to pin down the reason for this high number, we know it is not linked to the COVID-19 pandemic. The UK's response to the spread of avian influenza has been rapid, and from 29 November birds were required to be housed inside with additional biosecurity measures put in place such as foot dips and disinfecting clothing.

Testing and surveillance of wild birds have shown that there is a high prevalence of the virus in these birds currently, and this is contributing to the spread of disease to farm and domestic bird populations.

A more detailed look at the genetic make-up of these viruses shows that they are different to those from previous years. This is predicted to be as a result of the virus infecting multiple birds across a range of species, and this provides the perfect opportunity for the virus to evolve. Analysis of these genetic changes does not raise any alarm bells for increased transmission to humans, but they are likely impacting the spread and severity of disease in birds.

What should we do if we find a dead bird or are concerned about bird health?

If the public finds dead waterfowl birds they are encouraged not to touch them but to report them to Defra using the appropriate phone number that can be found on the website, also any other wild birds found dead in numbers of five or greater should be reported.

What is Pirbright doing to tackle this virus?

Researchers at Pirbright are attempting to enhance the control and detection of avian influenza in poultry populations as well as extend our basic knowledge about the virus in avian and mammalian hosts. The research groups led by Professor Munir Iqbal and Dr Holy Shelton are investigating how avian influenza virus strains originated from wild birds can rapidly adapt to cause disease outbreaks in poultry and gain the potential to infect humans. In addition, Professor Munir Iqbal is developing improved poultry vaccines that prevent virus replication and spread. These vaccines are particularly useful in countries where avian influenza is regularly found in the domestic poultry and the control and prevention of spread isn't easy, such as in the UK.
Year(s) Of Engagement Activity 2021
URL https://www.pirbright.ac.uk/news/2021/12/avian-influenza-tackling-large-numbers-outbreaks-winter-uk
 
Description BBSRC Partnering Seminar, University of Liverpool, Tamilnadu Veterinary and Animal Science University 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk presented entitled " Molecular determinants of antigenicity of H7 and H9 avian Influenza viruses". The research data shared with the colleagues working to reduce the impact of avian infectious diseases on poultry production. The discussion led to more collaboration and work together, acquiring reagents and protocols for further research and development activities.
Year(s) Of Engagement Activity 2019
 
Description Bird flu genetic make-up different from previous years 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Research outputs were mass comminated for the general public via a news story.

Lockdowns due to spreading viruses are continuing to affect UK poultry and captive bird owners and scientists say the latest research into this year's avian influenzas shows a different genetic make-up.

The number of outbreaks this year has been the most extensive ever across the UK with more than 50 cases, compared to just 26 last year. Testing and surveillance of wild birds have shown that there is a high prevalence of the virus currently in birds, and this is contributing to the spread of disease to farm and domestic bird populations.

Dr Holly Shelton, head of Pirbright's Influenza Viruses group, is looking at understanding how genetic changes in influenza A viruses can impact disease spread, host responses to infection and the pathology associated with the disease.

Shelton said avian influenza viruses are different to those that can infect humans in that they cannot easily infect and must change and adapt to do so. Aquatic birds are a natural reservoir for avian influenza viruses but typically experience fewer clinical symptoms despite spreading the disease to domestic birds in the migratory season between October and March.

Bird migration
Responding to questions on what was causing bird flu outbreaks in domestic birds, she said: "In the spring and summer months these birds spend their time breeding and raising their young in north-eastern Asia where they mix with other bird species. This enables virus transmission and mutation. Then, when they migrate for the autumn and winter months, they shed viruses in their faeces along the way. "One of the migratory paths is across northern Europe and this includes the UK. This year in the UK, avian influenza was first discovered on 15 October in captive aquatic birds. To date (17 December), there have been 50 outbreaks in England, 1 in Wales and 2 in Scotland. This has resulted in over half a million birds being destroyed to control the spread of the disease."

Testing and surveillance
Government testing and surveillance of wild birds have shown a high prevalence of the virus in these birds which was contributing to the spread of the disease to farm and other domestic bird populations. The Royal Society for the Protection of Birds said this week that avian influenza had already killed more than 850 barnacle geese at its Mersehead reserve near Dumfries.

"We are probably approaching 4,000 - certainly over 3,000 - mostly barnacle geese. It is pretty large scale and likely to get worse. It is unprecedented. I have worked in the area for 25 years and I don't ever remember us seeing this many birds dying," said the charity's area manager, Andrew Bielinski.

"A more detailed look at the genetic make-up of these viruses shows that they are different to those from previous years. This is predicted to be a result of the virus infecting multiple birds across a range of species, and this provides the perfect opportunity for the virus to evolve. "Analysis of these genetic changes does not raise any alarm bells for increased transmission to humans, but they likely impact the spread and severity of disease in birds."

Enhancing control
Research at Pirbright is looking at enhancing control and detection of avian influenza as well as extending knowledge about the virus in avian and mammalian hosts. The Influenza Viruses group is involved in the assessment of which avian influenza virus strains can rapidly adapt to cause potential infections of humans. In addition, Shelton's group is mapping the changes in the chicken respiratory and gastrointestinal microbiome following virus infection and assessing whether the application of probiotics can be useful in controlling virus shedding or transmission in birds.

The Influenza Group, led by Professor Munir Iqbal, is developing improved poultry vaccines that can prevent virus replication and spread. These vaccines are particularly useful in countries where avian influenza is regularly found in the domestic poultry and the control of prevention of spread isn't easy, such as the UK.
Year(s) Of Engagement Activity 2022
URL https://www.poultryworld.net/health-nutrition/bird-flu-genetic-make-up-different-from-previous-years...
 
Description Bird flu study from Pirbright Institute sheds light on mutations and health impacts 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Bird flu study from Pirbright Institute sheds light on mutations and health impacts. Emerging research from the Pirbright Institute shows that avian influenza mutations could increase disease threat to poultry, but make it less infectious for humans.

Mutations in the H7N9 bird flu virus increase its replication rate and stability in avian cells, but reduce its preference for infecting human cells, a study from The Pirbright Institute has found. The results show that outbreaks in birds caused by strains with these mutations could pose a lower risk to human health, while remaining a significant threat to the poultry industry.

H7N9 low-pathogenicity avian influenza (LPAI) virus usually infects birds, but in 2013 the first human case was recorded in China. Since then, there have been over 1,500 confirmed human infections with about 40 percent of cases resulting in fatalities. Further evolution of the H7N9 virus gave rise to a high-pathogenicity avian influenza (HPAI) strain that could cause 100 percent mortality in chickens. In 2017 the Chinese Government initiated a wide scale vaccination programme in chickens which drove down cases of both low and high pathogenicity strains.

Previous Pirbright research identified three mutations in avian influenza H7N9 viruses that enabled them to overcome immunity generated by vaccines. The mutations altered a protein on the outside of the virus called haemagglutinin (HA), which binds to host cell receptors and allows the virus to enter and cause infection.

In the latest study, published in the Journal of Virology, the team discovered the same mutations occurred in H7N9 viruses isolated from the field in 2019, which most likely emerged in birds that had either been immunised or naturally infected. Analysis of the viruses demonstrated that strains with these mutations have significantly increased replication rates in both chicken cell cultures and chick embryos as well as displaying greater acid and thermal stability, which could improve transmission ability.

The mutations also influenced which animal cells the strain could enter - their HA proteins could still bind to the receptors of bird cells, but they lost their affinity for human cell receptors. These findings show that in evolving to escape the chicken immune system, the mutated H7N9 viruses have reduced their risk to human health whilst increasing the threat they pose to poultry, although further studies in birds are needed to confirm the impact this could have on infection and disease spread.

Professor Munir Iqbal, head of the Avian Influenza Group at Pirbright, said: "Our approach has allowed us to accurately predict avian influenza mutations that appear in the field, and assess how these mutations could affect the risk they pose to both human and avian populations. This information can be used to inform surveillance efforts and provide early warnings of potentially dangerous emerging strains."
Year(s) Of Engagement Activity 2020
URL https://www.thepoultrysite.com/news/2020/07/bird-flu-study-from-pirbright-institute-sheds-light-on-m...
 
Description Combating avian influenza by developing novel diagnostic tools and vaccines. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Combating avian influenza by developing novel diagnostic tools and vaccines. ZELS grant holders and Stakeholders meeting in Tanzania 24-25 January 2017.

Progress report on BBSRC funded ZELS project on improvement of vaccines and diagnostics for avian influenza viruses to international experts working on the control of infectious diseases of livestock and poultry.
Year(s) Of Engagement Activity 2017
 
Description Deimante Lukosaityte: Microbiology Society conference 2019. Poster presentation: Chicken protection against H9N2 virus by passive immunization 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Described techniques for development of next generation of vaccines against viral diseases affecting animals and humans.
Year(s) Of Engagement Activity 2019
 
Description Demonstrating Mathematics (Angita Shrestha) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Angita Shrestha (PhD student within Avian Influenza group) provided help in a Maths session to the new Oxford Doctoral Training Porgramme (DTP) cohort.
Year(s) Of Engagement Activity 2018
 
Description Determinants of antigenicity of H9 Avian Influenza Viruses. UK-China Swine and Poultry Workshop.17-18 June 2019, The Pirbright Institute, UK. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The talk and the discussion on the improvement of disease control systems (vaccines and diagnostics) to prevent avian influenza viruses infection in poultry and zoonotic infections in humans.
Year(s) Of Engagement Activity 2019
 
Description Engineered Recombinant Single Chain Variable Fragment of Monoclonal Antibody Provides Protection to Chickens Infected with H9N2 Avian Influenza. Presented by Deimante Lukosaityte at Influenza Update meeting 4th - 15th December 2020: The University of Liverpool (online meeting) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The talk describes a technique for the development of immunotherapy to protect poultry from Infectious diseases such as avian influenza viruses. The talk provided evidence that recombinant antibodies can provide passive immunity to protect chickens from avian influenza. Several mAbs generated from mice hybridomas targeting hemagglutinin (HA) of H9N2 virus were converted into single-chain variable fragment (scFv) antibodies. Recombinant scFvs were purified from insect cell culture supernatants and showed it could retain neutralization capacity against H9N2 virus in vitro. To test therapeutic scFv efficacy in vivo we selected two of the recombinantly produced scFv antibodies for prophylaxis and treatment of chickens infected with H9N2 UDL-01 virus. Intranasally treated birds showed reduced disease manifestation and virus shedding. These results indicate that antibody therapy could be beneficial for the provision of rapid treatment for reducing disease impacts in poultry.
Year(s) Of Engagement Activity 2020
URL https://www.gla.ac.uk/researchinstitutes/iii/cvr/events/influenza/
 
Description Evolution of H9N2 avian influenza virus under immune pressure. Presented at 10th International Symposium on Avian Influenza, 15th - 18th April 2018, The Grand Hotel, Brighton, UK. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The primary aim of the workshop was to forge long-term research partnerships between early-career researchers, livestock industry and national disease control authorities in the UK and the Philippines. In addition, the activity hopes provide information about the emerging and next generation diagnostic and vaccine strategies and their utilization to reduce the impact of viral diseases on livestock and poultry.
Year(s) Of Engagement Activity 2019
URL https://www.slideshare.net/zerep_cire/2019-newton-agham-researcher-links-workshop-vaccines-and-diagn...
 
Description Evolutionary fitness of avian influenza viruses and development of improved vaccines and diagnostics. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Seminar entitled "Evolutionary fitness of avian influenza viruses and development of improved vaccines and diagnostics" was presented as invited speaker to Postgraduate students and staff at RVC (Hawkshead Campus), UK. 19 October 2016.
Year(s) Of Engagement Activity 2016
 
Description Evolutionary fitness of avian influenza viruses and development of improved vaccines and diagnostics. Seminar as inviated speaker at RVC (Hawkshead Campus), UK. 19 October 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Talk delivered on the topic "improvement of vaccines and diagnostic for poultry at The pirbright Institute UK, as an invited speaker at Royal Veterinary College (RVC) London
Year(s) Of Engagement Activity 2016
 
Description Genetic engineering speeds up poultry vaccine development 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Researchers report the rapid generation of a bivalent vaccine against Marek's disease and avian influenza

Scientists at The Pirbright Institute have used genetic engineering to develop a vaccine that protects birds against both Marek's disease and avian influenza. They say the process is faster and more efficient compared to previous methods, which will allow poultry vaccine producers to rapidly update vaccine strains in order to keep up with virus evolution.

In a study published in the journal Vaccines, the team used the gene editing tool CRISPR/Cas9 to insert an avian influenza gene into the turkey herpesvirus (HVT) that is used in Marek's disease vaccines. The gene codes for haemagglutinin (HA), an influenza protein that is key for virus entry into host cells and is therefore an important target of the host immune response to block infection.

"HVT is already widely used in vaccines against Marek's disease and can be administered to eggs, enabling automated delivery and providing birds with protection from the day they hatch. The additional HA gene we have incorporated will be expressed by HVT when it replicates in host cells, meaning that a single dose of vaccine induces immunity against both viruses", explained Professor Munir Iqbal, Head of the Avian Influenza group at Pirbright.

"The genetic engineering process we have developed using CRISPR/Cas9 is far quicker and more efficient than previous technologies, as well as being very consistent and accurate. These attributes are essential for providing fast and reliable vaccine production to protect poultry", Prof Iqbal added.

Mutations can occur with high frequency in HA proteins, enabling influenza viruses to evade immunity generated by vaccines. Using CRISPR/Cas9 to create new vaccines will help tackle evolving viruses by reducing the time it takes manufacturing companies to adapt their vaccine strains to match these mutations, allowing faster responses to outbreaks and providing better protection.

Although this gene editing method is very reliable, a small number of HVT viruses fail to incorporate the HA gene into their own genome effectively. To ensure HA is being expressed in the vaccine, the team exploited the HA protein's ability to bind to molecules on the surface of red blood cells.

Chicken cells infected with the successfully modified HVT virus express HA on their surface which red blood cells attach to, forming a clump that can be visualised using microscopy. This simple test improves the speed at which suitable vaccine candidates can be identified and has a much broader application as it can also be used for other viruses that incorporate proteins which interact with red blood cells.

"Improving how we make vaccines is critical for preventing avian influenza outbreaks. Our work could help reduce the spread of disease between birds and reduce the risk of infection for people who work closely with poultry", Prof Iqbal said. "Now that we have developed a rapid method for generating this modified vaccine, our next steps will be to study the vaccine's effectiveness in field trials."
Year(s) Of Engagement Activity 2020
URL https://www.cabi.org/vetmedresource/news/66612
 
Description H9N2 avian influenza viruses: impact of evolutionary changes on virus antigenicity, receptor binding and zoonotic potential. Presented at "Conference on Animal Infectious Diseases and Human Health" held at The Veterinary Biotechnology Branch of Chinese Association of Animal Science and Veterinary Medicine & the Veterinary Immunology Branch of Chinese Society for Immunology. August 7th-10th, 2018 Harbin, China. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Dissemination of research outcomes to prevent and control of infectious diseases of animals and humans.
- Avian influenza virus evolution and efficacy.
-
Year(s) Of Engagement Activity 2018
 
Description H9N2 avian influenza viruses: impact of evolutionary changes on virus antigenicity, receptor binding and zoonotic potential. Presented at "Conference on Animal Infectious Diseases and Human Health" held at The Veterinary Biotechnology Branch of Chinese Association of Animal Science and Veterinary Medicine & the Veterinary Immunology Branch of Chinese Society for Immunology. August 7th-10th, 2018 Harbin, China. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Focus of the conference was to improve control against infectious diseases affecting poultry and livestock.
Year(s) Of Engagement Activity 2018
 
Description High pathogenicity avian Influenza (HPAI) H5 in Europe -Epidemiology and Surveillance. Presented via Webinar, organized by Boehringer Ingelheim, 3rd July 2020. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk entitled; High pathogenicity avian Influenza (HPAI) H5 in Europe -Epidemiology and Surveillance. talk was organized by Boehringer Ingelheim, 3rd July 2020 and presented via Webinar.
Year(s) Of Engagement Activity 2020
 
Description How virus tracking can help us prevent future pandemics 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact UAR interviewed Professor Munir Iqbal, head of the Avian Influenza group at The Pirbright Institute, https://www.pirbright.ac.uk/users/prof-munir-iqbal.

The Pirbright Institute specialises in the research and diagnosis of livestock viral diseases and viruses that spread from animals to humans.

The Institute is part of an international network that tracks viruses and formulates ways to control and prevent outbreaks, such as creating new vaccines and better diagnostics.

While the Covid-19 pandemic grabs the headlines there are other, potentially more deadly viruses, spreading through the animal kingdom, which may have the capacity to infect humans.

Perhaps the most well-known pandemic agent - before Covid-19 - was the flu virus. The 1918 influenza pandemic, caused by an H1N1 virus of avian origin, was the most severe pandemic in recent history, infecting one-third of the world's population and killing at least 50 million worldwide. These viruses evolve, so every year the world is at risk of a new strain of flu. One related virus that caused the 2009 swine flu pandemic killed over 200,000 people worldwide.

Professor Munir Iqbal heads up the Avian Influenza Virus group at The Pirbright Institute. This group is imitating natural selection and evolution of influenza viruses in the lab. They hope to identify how viruses might change - potentially to be more dangerous. By identifying those changes they can make informed decisions about how to create vaccines against these potential new strains.

A new strain, H7N9, emerged in China in February 2013, infecting both poultry and humans. Since then, there have been over 1500 confirmed human infections from this strain with an estimated 40% fatality rate.

By 2017 the Chinese government had, very rapidly for a new vaccine, implemented a mass vaccination programme against H7N9 in poultry. This was accompanied by a striking reduction in human infection from this virus.

At first this seemed to be good news, but it turns out that suboptimal vaccine practices were creating an evolutionary pressure for the virus to change - to escape the effects of vaccination. As the virus evolved it didn't infect human populations so well, but it became more aggressive in the poultry, even if they had been vaccinated. Iqbal explains,

"At The Pirbright Institute, we study how these viruses evolve to persist in poultry and overcome vaccines, and how mutations impact virus virulence, transmission and, pathogenicity. Ultimately this will give us information on bird-to-human transmission and help develop diagnostic tools and vaccines to better fight the virus."

Disease transmission has to be studied in chickens but disease virulence can be quantified using chicken eggs. 14 day-old fertilised eggs are infected with the virus which then replicate. The faster the virus replicates in the embryo, the more virulent the strain.

"The quantity of virus being produced often equates to the aggressiveness of the disease. Very often viral infection depends on the amount of virus that you come in contact with. One particle might not infect animals or humans, but thousands could. In the same way, a smaller amount of virus might be needed to infect poultry compared to humans. We live alongside loads of virus without getting sick until we come across an amount large enough to cause an infection," explains Iqbal.

By imitating the natural selection process in the lab, the researchers identified the specific mutation that allowed the Chinese H7N9 virus to escape vaccine-induced immunity. They were also able to predict the evolution of influenza viruses. Three mutations that were observed in the lab have since been found in the field in 2019.

"These changes can have a huge impact in terms of virus transmission, virus virulence and virus transfusion across species from avian-to-human, avian-to-avian, or even to different mammalian species," adds Iqbal.

Fortunately for us, these three mutations prevent H7N9 viruses from binding to human cells, but increase their binding, replication and stability in chicken cells and embryos. This means that the strains that had evolved around the vaccination posed a lower threat to humans, but an increased risk to poultry. Mass vaccination of poultry against H7N9 strains in China might have been beneficial to humans, driving virus evolution away from a human pandemic, but it also meant that the evolved viruses posed an even greater threat to poultry.

However, this might not be the case for all strains warns Iqbal. Not all mutations that arise due to vaccine induced evolution, push viral strains away from human infection. In the future, other mutations may have human pandemic potential or be even more deadly to poultry.

Influenza viruses are a particular risk, as they infect a huge range of animals and mutate rapidly, which gives them the capacity to jump species and evade the immune system. They are particularly a cause for concern, because they circulate in livestock such as pigs and poultry which regularly come into close contact with humans.

Using a method that can predict how vaccination may change influenza virus characteristics is potentially valuable for making new vaccines against these fast evolving viruses. These predictions could also provide advanced warning of mutations that could increase likelihood of human infection.

Looking out for these viral mutations in the global health surveillance programme can help in the monitoring for potential threats. This might allow us to get ahead of them, by developing and using new vaccines, before new viral variants have a chance to spread and spiral out of control in a new pandemic.
Year(s) Of Engagement Activity 2020
URL https://www.understandinganimalresearch.org.uk/news/research-medical-benefits/how-virus-tracking-can...
 
Description Identification of antigenic epitopes to broaden and enhance the efficacy of avian influenza vaccines. Presented at 6th Animal Vaccines and immune Adjuvant Technologies Salon & Advanced seminar, Shandong-Binzhou Animal Science and Veterinary Medicine Academy, China, 18-20 October 2019. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The talk and the discussion was the best practices to improve control systems (vaccines and diagnostics) for prevention of avian influenza viruses infection in poultry and zoonotic infections in humans.
Year(s) Of Engagement Activity 2019
 
Description Immuno-pathobiology of H9N2 avian influenza viruses: looking at how the viruses evolve and persist in poultry. Presented at "Techniques for Healthy Farming and Diseases Prevention & Control of Livestock and Poultry. Beijing, August 13th-15th, 2018. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Dissemination of research outputs. Improvement of vaccines and diagnostics.
Year(s) Of Engagement Activity 2018
 
Description Improving vaccines and diagnostics for Avian influenza viruses affecting poultry. Presented at the International Poultry Expo "Poultry Science Conference", Lahore, Pakistan, 13-15 September 2019. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The talk and the discussion was the best practices to improve control systems (vaccines and diagnostics) for prevention of avian influenza viruses infection in poultry and zoonotic infections in humans.
Year(s) Of Engagement Activity 2019
 
Description Innovate Guildford (Angita Shrestha): 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact GENERAL SCIENCE
Year(s) Of Engagement Activity 2019
 
Description International Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Global Alliance for Research on Avian Diseases conference health in Hanoi 17-19 January 2018. Purpose of the conference was to establish global partnerships and links between academic researchers and the poultry industry to improve joined up work in regards to preventing, controlling and
combating avian diseases. The conferences provided a forum for discussion and exchange of ideas around the single theme of exploiting available opportunities to deal with emerging and existing infectious avian diseases in poultry production systems and to safeguard food supplies and human health.
Conference speakers discuused basic, applied and commercial aspects of research on avian diseases including:
• Evolution and Epidemiology of Avian Pathogens
• Host-Pathogen Interactions - Virulence and Pathogenicity
• Pathogen Mechanisms of Immune Evasion
• Next Generation Disease Control Strategies
• Vaccines
• Immunity
• Diagnostics
• Zoonoses and Socio-economic impacts of avian diseases
• Global Research Opportunities and Threats
Year(s) Of Engagement Activity 2018
URL http://www.theeventsportal.com/GARAD-2018/3/Home
 
Description Investigating avian influenza antigenic evolution and improving potency of poultry vaccines (Internal seminar) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact A talk presented describing how the genetic evolution of avian influenza viruses can result in vaccine failure and how we developed approaches that improve the effectiveness of poultry vaccines to reduce the economic loss in poultry.

We describe our research data H5 subtype of avian influenza viruses are evolving rapidly and being classified into different clades. These viruses carry significant antigenic heterogeneity and a single candidate vaccine may not be able to protect against the virus variants infecting poultry in different countries around the globe. Our data will allow for the generation of vaccines that are better strain-matched, thus reducing the impact of AIVs in the poultry industry.

We also present our work on the development of next-generation poultry vaccines termed "Targeted Antigen Delivery Vaccine (TADV)" that selectively deliver vaccine antigens to the chicken immune cells known as Antigen-presenting cells and potentiates immunogenicity of the vaccine.
Year(s) Of Engagement Activity 2022
 
Description Latest Pirbright collaboration uncovers genetic markers that could guide avian influenza surveillance 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Research outputs were mass comminated for the general public via a news story. This was published online at the Pirbright Institute webpage and One Health Poultry Health webpage and distributed wildly on social media including Facebook, Twitter, In Share.

Researchers at The Pirbright Institute have identified the genetic markers on avian influenza ('bird flu') viruses that could help the viruses to jump the species barrier and cause disease in people, in collaboration with other members of the One Health Poultry Hub.

Co-investigators Professor Munir Iqbal and Dr Joshua Sealy worked with scientists at Imperial College London, the University of Glasgow and The Francis Crick Institute, to show how the genetic traits of avian influenza H9N2 viruses influence their preference for infecting bird or human cells.

The paper detailing their findings, 'Genetic determinants of receptor-binding preference and zoonotic potential of H9N2 avian influenza viruses' is published in the Journal of Virology.

The research identifies genetic traits that alter a key H9N2 viral protein, called haemagglutinin, that makes it easier for the virus to recognise and bind to different cell receptors. This is the first step of viral infection, and the general inability of avian influenza viruses to effectively bind to human receptors is a major reason why they do not, in general, jump the species barrier to people.

However, given that human infections with H9N2 have been detected on an almost monthly basis since 2015, there may be a capacity for these viruses to evolve and gain the ability to efficiently target cellular receptors in people.

This latest discovery reveals which haemagglutinin properties of existing H9N2 strains allow them to bind to human receptors more effectively. These included small genetic differences as well as the overall structure and charge of the haemagglutinin protein. These findings will help guide future avian influenza surveillance by providing the genetic markers that signify the emergence of viruses with the potential to transmit to people.

There have been more than 60 cases recorded of people infected with H9N2 influenza viruses to date in 2020, all in countries where the virus is endemic. However, these viruses have not adapted to spread efficiently from person to person, a key element of a virus that has the potential to cause a pandemic.

Professor Iqbal and his team at Pirbright have previously described H9N2 viruses which showed a preference for human-like receptors.

Professor Iqbal said: "Understanding more about which traits increase the likelihood of H9N2 viruses jumping into humans help to identify viruses that could pose a future threat. Keeping an eye on viruses with these traits can help us to be prepared in the event that one of them evolves to pass between people rather than only from birds to humans."



This research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) the Medical Research Council (MRC) both part of UK Research and Innovation (UKRI).
Year(s) Of Engagement Activity 2021
URL https://www.pirbright.ac.uk/news/2021/01/latest-pirbright-collaboration-uncovers-genetic-markers-cou...
 
Description Lorin Adams (Gordon's School Careers Fair) 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Describe the research that lead to improve control systems against infectious viral diseases of animals and from animals to humans.
Year(s) Of Engagement Activity 2019
 
Description Mapping antigenic determinants of H9N2 avian influenza viruses and improving vaccines and diagnostics" presented at Foreign Talent Lecture: New strategies and new techniques for the prevention and control of major avian diseases. Shandong Binzhou Animal Science & Veterinary Medicine Academy, Binzhou, China. 6th August 2018. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The focus of the meeting was to improve the control systems against poultry diseases including development of improved vaccines and diagnostics
Year(s) Of Engagement Activity 2018
 
Description Molecular Determinants for Antigenicity and Vaccine Efficacy of H9 and H7 Avian Influenza Viruses. Newton Agham Researcher Links Workshop: Novel vaccines and diagnostics technologies against Emerging and re-emerging veterinary Pathogens. 4-7 February 2019 at Rizal Pak Hotel, Manila, Philippines. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The talk and the discussion on the improvement of disease control systems (vaccines and diagnostics) to prevent avian influenza viruses infection in poultry and zoonotic infections in humans.
Year(s) Of Engagement Activity 2019
 
Description Molecular determinants modulating avian influenza H7N9 virus antigenicity. Presented at The Microbiology Society Annual Conference 2019, 8-11 April ICC Belfast, UK. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The talk and the discussion on the improvement of disease control systems (vaccines and diagnostics) to prevent avian influenza viruses infection in poultry and zoonotic infections in humans.
Year(s) Of Engagement Activity 2019
 
Description Molecular determinants of antigenicity of H7 and H9 avian Influenza viruses. Presented as invited speaker at BBSRC UK-India Partnering Award seminar: University of Liverpool. 2 May 2019. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The talk and the discussion on the improvement of disease control systems (vaccines and diagnostics) to prevent avian influenza viruses infection in poultry and zoonotic infections in humans.
Year(s) Of Engagement Activity 2019
 
Description Munir Iqbal: Cheltenham Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Describe the research that lead to improve control systems against infectious viral diseases of animals and from animals to humans.
Year(s) Of Engagement Activity 2019
 
Description New rapid protection bird flu vaccine 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Research outputs were mass comminated for the general public via a news story. This was published online on Poultry world (Poultry World edition 10 of 2021 now online) entitled. New rapid protection bird flu vaccine.

Professor Munir Iqbal, head of the Avian Influenza Virus group at Pirbright Institute, speaks to Poultry World about the potential of an improved poultry influenza vaccine that triggers a rapid immune response that protects chickens against signs of disease and reduces the amount of virus that they could pass on.
Year(s) Of Engagement Activity 2021
URL https://content.yudu.com/web/1r3p1/0A1zifp/PoultryWorld2021-10/html/index.html?origin=reader&page=30
 
Description Newton Agham Researcher Links Workshop on "Novel Vaccines and Diagnostic Technologies Against Emerging and Re-emerging Veterinary Pathogens, Rizal Park Hotel, Manila, Philippines 4-7 February 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The primary aim of this workshop was to forge long-term research partnerships between early-career researchers, livestock industry and national disease control authorities in the UK and the Philippines. The workshop provided information on emerging and next generation diagnostic and vaccine strategies and their utilization to reduce the impact of viral diseases on livestock and poultry.
Year(s) Of Engagement Activity 2019
URL https://www.slideshare.net/zerep_cire/2019-newton-agham-researcher-links-workshop-vaccines-and-diagn...
 
Description Next-generation poultry vaccines, presented by Munir Iqbal to the The Pirbright Institute Trustee Board and Science Advisory Board meeting on 20th July 2021. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Policymakers/politicians
Results and Impact Data was presented to the Pirbright Institute senior management on the development and potency of a new improved vaccine to protect poultry from avian influenza viruses. The new vaccine carries the potential to triggers a rapid immune response that protects chickens against signs of disease and reduces the level of virus that they could pass on, a key element to halting the spread of bird flu through flocks. The vaccine would also be easier and less costly to produce than the traditional flu vaccines made in chicken eggs. This vaccine is now being evaluated for large scale commercial production and deployment in the field.
Year(s) Of Engagement Activity 2021
URL https://www.pirbright.ac.uk/news/2021/07/pirbright%E2%80%99s-new-bird-flu-vaccine-provides-rapid-pro...
 
Description Pengxiang Chang: Talk presentation:The application of CRISPR/Cas9 system in the generation of viral vectored avian influenza vaccines at Microbiology Society conference, UK. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The talk and the discussion on the improvement of vaccines to prevent avian influenza viruses infection in poultry and zoonotic infections in humans.
Year(s) Of Engagement Activity 2019
URL https://microbiologysociety.org/event/annual-conference/annual-conference.html
 
Description Pengxiang Chang:Influenza update meeting. The application of CRISPR/Cas9 in the development of vaccines against avian influenza virus 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Described techniques to improve and produce new effective vaccines against viral diseases of animals and humans.
Year(s) Of Engagement Activity 2019
 
Description Pirbright Institute research teams studying characteristics of influenza virus that may alter disease outcomes in poultry. 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Avian influenza, commonly known as "bird flu," is a disease caused by multiple strains of influenza virus. The viruses can infect a wide range of animals, including people and pigs, but the natural reservoir lies in populations of wild aquatic birds such as ducks and gulls, according to an announcement from The Pirbright Institute in the U.K., which is conducting research to better understand avian influenza viruses to help prevent the disease in poultry.

Flu virus strains are categorized by the combination of the two proteins found on the outside of the virus: hemagglutinin (H) and neuraminidase (N) -- for example, H5N6 or H9N2. The H protein binds to cell receptors in order to initiate infection, while the N protein helps release new viruses from an infected cell, the institute explained.

Strains are also classified by severity. Low-pathogenic avian influenza (LPAI) viruses cause clinical signs such as mild breathing problems, decreased egg production and growth. Some birds, particularly ducks and geese, do not display any signs of LPAI infection and are still able to spread the disease, Pirbright said. When LPAI viruses circulate in high-density poultry areas, the viruses can mutate into highly pathogenic strains.

Highly pathogenic avian influenza (HPAI) viruses have severe and often fatal effects on some species of birds such as chickens, Pirbright noted, but some HPAI strains cause mild or no clinical signs of disease in wild birds and domestic waterfowl. These strains are notifiable, meaning government control measures must be put in place.

Avian influenza can be carried vast distances by wild migratory birds and can infect domesticated poultry through direct contact or through contaminated droppings and bodily fluids, Pirbright said. Because of this, there is a year-round risk of avian influenza, which can increase depending on the disease status in a region and the migration season of wild aquatic birds.

According to Pirbright, good biosecurity is essential in preventing poultry from being exposed to the disease and can be practiced on a commercial farm, with game birds or even with just a few backyard hens.

Why is influenza so difficult to prevent?

The institute explained that influenza viruses are constantly changing, and when they replicate, small errors called mutations are copied into their genome. Some of these will alter the virus's proteins, allowing the virus to escape detection by the immune system.

All flu viruses also have the potential to undergo a process called reassortment, where two or more strains of influenza infect the same animal, allowing them to swap parts of their genome, Pirbright said. The resulting viruses can potentially have different characteristics than the original strains, such as the ability to replicate in different species, including people, the institute added.

Avian influenza viruses such as H5N1 or H7N9 have infected people, predominantly in Southeast Asia, but in these cases, the virus has been transmitted directly from infected birds to people, with no onward spread. There is some evidence that avian influenza can be passed from person to person, and while there are no records of efficient or sustained human transmission, there is a constant risk that one of the new strains may spread easily among people, which could result in a new influenza virus pandemic, Pirbright said.

Changes in the virus genetics from mutation or reassortment make it very difficult to anticipate how influenza viruses will spread through a population and whether current vaccines will be suitable for the strains that are circulating, Pirbright announced.

The influenza research programs at Pirbright are progressing understanding of the virus and finding better ways to prevent its spread.

Pirbright Institute group leaders Dr. Holly Shelton and professor Munir Iqbal are researching how the characteristics of influenza viruses can change the outcomes of disease. Studying flu at the molecular level allows them to find out how the virus evolves to overcome avian immunity and how changes in their genome can alter disease severity and their ability to affect different species, the announcement said.

Shelton's and Iqbal's teams are working on identifying genetic markers for specific disease traits that can be used in surveillance systems to provide forewarning of strains that could cause pandemics. For example, Shelton's Influenza Viruses group is looking at which characteristics allow the viruses to become resistant to antiviral drugs that are currently used to treat human infections of influenza, allowing surveillance to provide an early warning of viruses that could cross into humans and be difficult to control, Pirbright said.

The team is also investigating how long it takes for avian influenza viruses to adapt to new mammalian species. According to the institute, establishing which strains can rapidly adapt and identifying the genetic changes made to enable infection of mammalian cells will help with surveillance efforts and potentially lead to the development of techniques that will help prevent these mutations occurring.

Vaccination and rapid diagnosis are very important for influenza prevention and control, but it is still not currently possible to protect against all influenza strains, Pirbright said, noting that Iqbal's Avian Influenza group is exploring which sites on the virus trigger the chicken immune system to respond quickly and fight off infection. This will better inform scientists' ability to match vaccines to strains in the field and could help to develop vaccines that are more effective.

Iqbal's group is also developing multivalent vaccines that protect chickens and ducks from several avian influenza subtypes at once as well as test kits for rapid diagnosis of different subtypes at the flock-side, the announcement said.

Visit Pirbright's Influenza Viruses and the Avian Influenza group pages to find out more about their research.

Source: The Pirbright Institute, which is solely responsible for the information provided and is wholly owned by the source. Informa Business Media and all its subsidiaries are not responsible for any of the content contained in this information asset.
Year(s) Of Engagement Activity 2019
URL https://www.feedstuffs.com/nutrition-health/protecting-poultry-avian-influenza
 
Description Poultry Stakeholders meeting hosted by Al Dousari Veterinary Services and Agriculture Co (Qatar ) in Qatar, 15 October 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The focus of talk was best practices for prevention and control of Avian influenza disease outbreaks in poultry

Vaccines and diagnostics for the control of avian influenza in poultry
Year(s) Of Engagement Activity 2019
 
Description Poultry Stakeholders meeting hosted by Almarai, 15 October 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Engagement with Almarai Poultry. The focus of the meeting with Almarai Poultry disease control team was to share knowledge on improved vaccination and diagnostic techniques against avian influenza viruses affecting poultry production.
Year(s) Of Engagement Activity 2019
 
Description Poultry Stakeholders meeting in Kuwait city 16 October 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Prevention and control of avian influenza outbreaks in poultry.
Described new vaccination and diagnostic technologies that provide more robust cross-protective immunity in emerging antigenic divergent strains of avian influenza viruses.
Year(s) Of Engagement Activity 2019
 
Description Preventing a future pandemic by imitating natural selection 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact By Munir Iqbal
A new type of avian influenza that can infect poultry and humans, called H7N9, emerged in China in February 2013. Since then, there have been over 1500 confirmed human infections with an estimated 40% case fatality rate.

In the wake of COVID-19, these numbers may seem to be relatively small. But these statistics provide an example of the issues we face in controlling influenza viruses in animals and how understanding more about these viruses can help us to predict, prevent and control outbreaks, protecting both poultry and human health.

Influenza viruses infect a huge range of animals, but the strains that are of greatest concern to us are those that circulate in livestock such as pigs and poultry, where people in farming industries have close contact with the animals. Influenza viruses can rapidly mutate, allowing them to escape the immune responses of the animals they infect and even jump to new species.

There have been five major epidemic waves of H7N9 in China. The final wave in 2016-2017 saw the originally mild disease of poultry mutate to cause higher levels of mortality in chickens and spread almost everywhere in China. The severity of H7N9 AIV situation prompted the Chinese government to implement a mass vaccination programme against H7N9 in poultry in 2017.

Since its use, the number of poultry outbreaks along with human infections has dropped dramatically, with only three human infection cases reported during 2017 to 2018 and one human infection case reported during 2018 to 2019. This may sound like vaccination has solved the problem and the virus will now be eradicated. Unfortunately, this is not the case - despite the reduction in disease outbreaks due to vaccination, these viruses have not been eradicated.

This is partly because of influenza's high mutation rate - vaccination can inadvertently encourage the evolution of viruses with mutations that allow them to escape vaccine-induced immunity. Once a virus escapes, it can spread rapidly, thereby making the vaccine ineffective and a new one must be designed. This is where our research comes in.

Our aim is to understand how H7N9 viruses could potentially mutate in the field in response to vaccination, and how these genetic changes could alter how the virus acts (for example, by making it more dangerous to poultry or by helping it to infect humans more effectively).

By imitating the natural selection process in the lab, we found several mutations and identified that one specific mutation allows the virus to escape from vaccine-induced immunity. Importantly, three other mutations that we observed in our lab studies had been found in the field in 2019 indicating that our method can predict the evolution of influenza viruses.

These three mutations prevent H7N9 viruses from binding to human cells, but increase their binding, replication and stability in chicken cells and embryos. This could mean that the strains which have these mutations pose a lower threat to human health, but increase the risk to poultry.

This shows that mass vaccination of poultry against H7N9 strains in China drives virus evolution away from human pandemic. But viruses with 'escape mutations' remain a significant risk to poultry due to their ability to escape vaccine-induced immunity and persist in poultry.

Our studies may also help to explain the Chinese government's successful control of H7N9 infection in humans by mass poultry vaccination. On one hand, the mass poultry vaccination protects the poultry from H7N9 infection and greatly reduces the risk of human infections as the majority of human H7N9 cases are linked to exposure to infected poultry or contaminated environments. On the other hand, even when some viruses escape the vaccine-induced immunity, they pose reduced risk to humans due to the lost human receptor binding.

However, this may not be the case for all strains. Other mutations may arise in the future that have human pandemic potential or are even more deadly to poultry. Using a method that can predict how vaccination may change influenza virus characteristics is hugely valuable as it can provide advanced warning of mutations that could increase likelihood of human infection. Incorporating these mutations into global health surveillance efforts can help relevant authorities to monitor potential threats and get ahead of them before they have a chance to spiral out of control.
Professor Munir Iqbal is head of the Avian Influenza Group at The Pirbright Institute.
Year(s) Of Engagement Activity 2020
URL https://www.newton-gcrf.org/impact/data-insights-blog/preventing-a-future-pandemic-by-imitating-natu...
 
Description Protecting poultry from avian influenza 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Avian influenza, commonly known as "bird flu," is a disease caused by multiple strains of influenza virus. The viruses can infect a wide range of animals, including people and pigs, but the natural reservoir lies in populations of wild aquatic birds such as ducks and gulls, according to an announcement from The Pirbright Institute in the U.K., which is conducting research to better understand avian influenza viruses to help prevent the disease in poultry.

Flu virus strains are categorized by the combination of the two proteins found on the outside of the virus: hemagglutinin (H) and neuraminidase (N) -- for example, H5N6 or H9N2. The H protein binds to cell receptors in order to initiate infection, while the N protein helps release new viruses from an infected cell, the institute explained.

Strains are also classified by severity. Low-pathogenic avian influenza (LPAI) viruses cause clinical signs such as mild breathing problems, decreased egg production and growth. Some birds, particularly ducks and geese, do not display any signs of LPAI infection and are still able to spread the disease, Pirbright said. When LPAI viruses circulate in high-density poultry areas, the viruses can mutate into highly pathogenic strains.

Highly pathogenic avian influenza (HPAI) viruses have severe and often fatal effects on some species of birds such as chickens, Pirbright noted, but some HPAI strains cause mild or no clinical signs of disease in wild birds and domestic waterfowl. These strains are notifiable, meaning government control measures must be put in place.

Avian influenza can be carried vast distances by wild migratory birds and can infect domesticated poultry through direct contact or through contaminated droppings and bodily fluids, Pirbright said. Because of this, there is a year-round risk of avian influenza, which can increase depending on the disease status in a region and the migration season of wild aquatic birds.

According to Pirbright, good biosecurity is essential in preventing poultry from being exposed to the disease and can be practiced on a commercial farm, with game birds or even with just a few backyard hens.

Why is influenza so difficult to prevent?

The institute explained that influenza viruses are constantly changing, and when they replicate, small errors called mutations are copied into their genome. Some of these will alter the virus's proteins, allowing the virus to escape detection by the immune system.

All flu viruses also have the potential to undergo a process called reassortment, where two or more strains of influenza infect the same animal, allowing them to swap parts of their genome, Pirbright said. The resulting viruses can potentially have different characteristics than the original strains, such as the ability to replicate in different species, including people, the institute added.

Avian influenza viruses such as H5N1 or H7N9 have infected people, predominantly in Southeast Asia, but in these cases, the virus has been transmitted directly from infected birds to people, with no onward spread. There is some evidence that avian influenza can be passed from person to person, and while there are no records of efficient or sustained human transmission, there is a constant risk that one of the new strains may spread easily among people, which could result in a new influenza virus pandemic, Pirbright said.

Changes in the virus genetics from mutation or reassortment make it very difficult to anticipate how influenza viruses will spread through a population and whether current vaccines will be suitable for the strains that are circulating, Pirbright announced.

The influenza research programs at Pirbright are progressing understanding of the virus and finding better ways to prevent its spread.

Pirbright Institute group leaders Dr. Holly Shelton and professor Munir Iqbal are researching how the characteristics of influenza viruses can change the outcomes of disease. Studying flu at the molecular level allows them to find out how the virus evolves to overcome avian immunity and how changes in their genome can alter disease severity and their ability to affect different species, the announcement said.

Shelton's and Iqbal's teams are working on identifying genetic markers for specific disease traits that can be used in surveillance systems to provide forewarning of strains that could cause pandemics. For example, Shelton's Influenza Viruses group is looking at which characteristics allow the viruses to become resistant to antiviral drugs that are currently used to treat human infections of influenza, allowing surveillance to provide an early warning of viruses that could cross into humans and be difficult to control, Pirbright said.

The team is also investigating how long it takes for avian influenza viruses to adapt to new mammalian species. According to the institute, establishing which strains can rapidly adapt and identifying the genetic changes made to enable infection of mammalian cells will help with surveillance efforts and potentially lead to the development of techniques that will help prevent these mutations occurring.

Vaccination and rapid diagnosis are very important for influenza prevention and control, but it is still not currently possible to protect against all influenza strains, Pirbright said, noting that Iqbal's Avian Influenza group is exploring which sites on the virus trigger the chicken immune system to respond quickly and fight off infection. This will better inform scientists' ability to match vaccines to strains in the field and could help to develop vaccines that are more effective.

Iqbal's group is also developing multivalent vaccines that protect chickens and ducks from several avian influenza subtypes at once as well as test kits for rapid diagnosis of different subtypes at the flock-side, the announcement said.

Visit Pirbright's Influenza Viruses and the Avian Influenza group pages to find out more about their research.

Source: The Pirbright Institute, which is solely responsible for the information provided and is wholly owned by the source. Informa Business Media and all its subsidiaries are not responsible for any of the content contained in this information asset.
Year(s) Of Engagement Activity 2019
URL https://www.feedstuffs.com/nutrition-health/protecting-poultry-avian-influenza
 
Description Protecting poultry from avian influenza through passive immunisation. Presented at Foreign Experts Seminar "New strategies and new tools for the prevention and control of major poultry diseases. Shandong-Binzhou Animal Science and Veterinary Medicine Academy, China, 20-22 September 2019. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The talk and the discussion was the best practices to improve control systems (vaccines and diagnostics) for prevention of avian influenza viruses infection in poultry and zoonotic infections in humans.
Year(s) Of Engagement Activity 2019
 
Description Rebecca Daines: Cheltenham Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Described the research undertaken at the Pirbright Institute that lead to improve control systems against infectious viral diseases of animals and from animals to humans.
Year(s) Of Engagement Activity 2019
 
Description Recombinant single chain variable fragment (scFv) antibody protects chickens from avian influenza. Presented at Systems Immunology Workshop: Adaptive immune repertoires and beyond. 16th-17th January 2020. University of Surrey, UK 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A talk entitled "Recombinant single chain variable fragment (scFv) antibody protects chickens from avian influenza" was presented at the workshop exploring new technical advances for analysis and production of antibodies for prophylaxes and treatment of animal and humans diseases. Both academics and staff linked with animal and public health industry attended this workshop.
Year(s) Of Engagement Activity 2020
 
Description Researchers at Pirbright investigate the emergence of new bird flu viruses with the potential to infect people 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Following the news brief of our research outcomes for the general public and media was published on The Pirbright Institute and widely distributed through social media platforms including Facebook, Twitter, Linkedin.

Pirbright scientists have discovered that infection with two strains of avian flu can lead to the emergence of a new virus strain with the potential to jump from birds to humans.

Human cases of avian influenza are extremely rare but can occur if a person comes into very close contact with an infected or dead bird.

The study shows that avian influenza virus strains H9N2 and H7N9 can share genetic information to create an H9N9 strain with the potential to cause more severe disease in poultry and pose a threat to human health.

Avian influenza, also known as 'bird flu', is a type of influenza that spreads among birds. The UK faces a seasonal increase in the risk of avian influenza outbreaks which are associated with the migration patterns of wild birds.

Avian influenza is found across the globe, and in countries where multiple strains circulate it is important to monitor the emergence of new strains. Low virulence H9N2 and H7N9 circulate in poultry in Asia but do not cause severe disease. However, they are known to swap genetic information which can result in the emergence of an H9N9 strain, which can cause severe disease.

In collaboration with the Animal and Plant Health Agency (APHA), researchers at Pirbright discovered that the H9N9 strain was able to multiply significantly better in poultry cells, indicating the potential to cause more severe disease. They also discovered that it had a higher replication rate in human cells and could bind to these cells better than H9N2. The H9N9 strain can infect and transmit between ferrets highlighting the potential to cause disease in humans.

The study, published in the Journal of Virology, shows that strains already circulating in poultry populations can exchange genetic material, leading to the creation of new strains. This increases the risk of the virus jumping from avian hosts to humans and other mammals. The study concludes that H7N9 and H9N2 viruses circulating in the same regions pose a pandemic threat, which demonstrates the need for constant monitoring for the emergence of new virus strains.
Professor Munir Iqbal, Head of the Avian Influenza Group at Pirbright said: "This is the first study to show that infection with circulating H9N2 and H7N9 influenza viruses could create new virus strains such as H9N9 that cause more disease in poultry and pose a greater risk to human health. If a host is infected with two different strains, there is always a chance that they will swap genetic material to create a new strain. When this happens, it could lead to many outcomes, for example, the virus becoming more or less able to cause disease in a host, or a virus acquiring the ability to jump between hosts. This leads to viruses that primarily cause disease in animals having the ability to infect humans, which is what we have observed in this study. More research is needed to determine which avian flu viruses could combine and pose a threat to poultry and human health."

This study was supported by grants funded by the UK Research and Innovation Biotechnology and Biological Sciences Research Council under Newton Fund UK-China-Philippines-Thailand Swine and Poultry Research Initiative and Zoonoses and Emerging Livestock Systems (ZELS) with grants from FCDO and Dstl. The work was also funded by the GCRF One Health Poultry Hub and Defra (UK, including the Devolved Administrations of Scotland and Wales).
Year(s) Of Engagement Activity 2022
URL https://www.pirbright.ac.uk/news/2022/01/researchers-pirbright-investigate-emergence-new-bird-flu-vi...
 
Description Sushant Bhat:Pirbright Dragon Fair 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Described the research undertaken at the Pirbright Institute that lead to improve control systems against infectious viral diseases of animals and from animals to humans.
Year(s) Of Engagement Activity 2019
 
Description Sustainable poultry (meat and eggs) production in Pakistan: Challenges and Opportunities. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Discussion on sustainable poultry (meat and eggs) production in Pakistan: Challenges and Opportunities. Presented at UKRI-GCRF "Food Security, Agriculture, and Nutrition" workshop, Marriott Hotel, Islamabad, Pakistan. 9th- 10th March 2020.
organised by UKRI GCRF team.
The outcomes include the establishment of collaborative links with key stakeholders including policymakers and disease control officials. Closer links were established with official responsible for animal health and food security officials including Minister for Science and Technology of Pakistan, High commissioner of UK High Commission in Pakitan. Discussion agenda and key outcomes were also communicated to the President of Pakistan, Chairman of Higher Education Commission Pakitan and representatives from FAO and UKRI GCRF team.
Year(s) Of Engagement Activity 2020
URL https://www.thenews.com.pk/print/626768-upsign-network-ukri-to-organise-global-development-workshops
 
Description The Pirbright Village Duck Fair held on 16 June 2018 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Local Village Fair, interaction with local residence to expanse research aims and activities of The Pirbright Institute and benefits to UK and around the globe to prevent and control infectious diseases of animals and humans.
Year(s) Of Engagement Activity 2018
 
Description The co-Circulation of Low and High-path-AIV in the same country with sub-optimal bio-security: Virus evolution and impact on vaccine efficacy. Presented at the 11th Scientific conference of Egyptian Veterinary Poultry Association, Conference "Towards a National strategy to control poultry industry problems in Egypt". 20-23 April 2019. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The talk and the discussion on the improvement of disease control systems (vaccines and diagnostics) to prevent avian influenza viruses infection in poultry and zoonotic infections in humans.
Year(s) Of Engagement Activity 2019
 
Description The global Situation and pathobiology of Avian Influenza in different Avian Species. Presented at the 11th Scientific conference of Egyptian Veterinary Poultry Association, Conference "Towards a National strategy to control poultry industry problems in Egypt". 20-23 April 2019.. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The talk and the discussion on the improvement of disease control systems (vaccines and diagnostics) to prevent avian influenza viruses infection in poultry and zoonotic infections in humans.
Year(s) Of Engagement Activity 2019
 
Description The rise and fall of antigenic mutations: A path to the persistence of avian influenza viruses. The Pirbright Institute Research Update Seminar Series. 27th April 2021. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact A seminar at the Pirbright Institute Research Update Seminar Series. 27th April 2021. The research outcomes were discussed detailing how the avian influenza viruses (H9 subtype) evolve under vaccine immune pressure to sustain their fitness in poultry. Described the evolutionary genetic markers that significantly change the virus antigenicity which ultimately reduce the effectiveness of poultry vaccines against avian influenza viruses affecting poultry and huamns.
Year(s) Of Engagement Activity 2021
 
Description UK-China Philippines-Thailand Swine and Poultry Research Initiative project kick-off workshop" at China Agriculture University, Beijing, 26th-28th September 2018. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Emerging new approaches were discussed for prevention and control of infectious diseases affecting swines and poultry.
Year(s) Of Engagement Activity 2018
 
Description Understanding Antigenic Diversity, Zoonotic potential and immunological prevention of avian influenza viruses affecting poultry. Presented at "UK-China Philippines-Thailand Swine and Poultry Research Initiative project kick-off workshop" at China Agriculture University, Beijing, 26th-28th September 2018. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Meeting focus was to share research plans funded under "UK-China-Philippines-Thailand Swine and Poultry Research Initiative". Research projects investigate pathogens, zoonotic pathogens or "commensals" associated with food safety issues affecting poultry and swine.
Year(s) Of Engagement Activity 2018
URL https://bbsrc.ukri.org/funding/filter/joint-swine-poultry-initiative/
 
Description Understanding antigenic diversity, zoonotic potential and immunological prevention of avian influenza viruses affecting poultry. Presented at UK-China-Philippines-Thailand Swine and Poultry Research Initiative: Interim Project Workshop 13th-15th January 2020 Hilton Hotel, Bracknell, UK 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Outcomes of the research project entitled "Understanding antigenic diversity, zoonotic potential and immunological prevention of avian influenza viruses affecting poultry" were presented to colleagues working on prevention and control of infectious diseases affecting animals and humans. the work led to incite further research collaborations with different groups from UK, China, Thailand and Philippine.
Year(s) Of Engagement Activity 2020
 
Description Understanding avian influenza virus evolution and development of next generation vaccines. Presented at 459th Scientific Meeting of The Veterinary Research Club at The Farmers Club, 3 Whitehall Court London Friday 14th February 2020. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A talk presented entitled"Understanding avian influenza virus evolution and development of next generation vaccines". The discussion with senior staff from DEFRA and UKRI- BBSRC, researchers and veterinary professional like with control and prevention of animal diseases in United kingdom
Year(s) Of Engagement Activity 2020
 
Description Understanding avian influenza virus evolution, antigenic diversity and vaccine failure. Presented at the 2019 Symposium on techniques for healthy breading and disease prevention & control of livestock and poultry, Golden Harbor Hotel, Beijing, 21-23 August 2019. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk and discussion on the control of infectious animal diseases including avian influenza.
Year(s) Of Engagement Activity 2019
 
Description Visit to Cairo Poultry Company (CPC) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Industry/Business
Results and Impact Discussion and talk on prevention and control of poultry diseases (avian influenza and Newcastle Disease) and molecular factors affecting vaccine efficacy. The discussion and talk to present data, describing factors the directly influence protective efficacy of in use vaccines, and how they evaluate/ test vaccine failure.
Year(s) Of Engagement Activity 2019
 
Description Visit to Dakahlia Poultry Egypt 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Industry/Business
Results and Impact Discussion and talk presented at Dakahlia Poultry Egypt head office to workers involved in poultry production. The talk amis were to provide update on the impact of evolutionary genetic changes in the avian influenza and Newcastle disease viruses on the efficacy of vaccines and diagnostics. The molecular changes in virus genetic makeup allow virus to escape from vaccine induced immunity results vaccine and diagnostics failure. Consequently the avian influenza viruses continue to circulates in vaccinated flocks.
Year(s) Of Engagement Activity 2019
 
Description Why vaccines matter in the fight against zoonotic diseases 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A news story was published to increase the awareness of Zoonotic diseases and their impact on public health, food security, the economy and the environment.
This was publicised at The Pirbright Institute webpage and One Health Poultry Health webpage and distributed wildly on social media including Facebook, Twitter, In Share.
On World Zoonoses Day, Pirbright's Professor Munir Iqbal and Dr Joshua Sealy consider 600 years of developing technology to fight infectious diseases:
The history of human and animal immunisation against infectious disease begins with the Chinese practice of variolation in the fifteenth century. Here, infectious material was taken from one patient and inoculated into a non-infected patient to initiate a mild but protective infection.

Roughly 200 years later, Edward Jenner transformed the field of immunology by developing the world's first vaccine which involved immunising patients against smallpox using the closely related cowpox.

Fast-forward another 200 years and the application of vaccines had transformed. On 6 July 1885, now celebrated as World Zoonoses Day, Louis Pasteur successfully administered the first vaccine against rabies - and within decades myriad other diseases had also been tackled effectively, including diphtheria, tetanus, anthrax, cholera, plague, typhoid, tuberculosis, measles, mumps, rubella, and polio. Many of these pathogens had been infecting humans for years, and continue to do so where vaccines are not deployed.

Now, in the 21st century, vaccine research is undergoing another seismic shift.

In 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes COVID-19), emerged in humans which is believed to have originated in animals (known as zoonoses). It has since developed into the devastating COVID-19 pandemic and in doing so it triggered an urgent need to develop vaccines to control a virus that represents a growing problem at the human-animal interface.

Pathogen evolution:
Broadly speaking, humans have a naïve immune system to the many pathogens that exclusively circulate within animal reservoirs, including livestock. Most pathogens have evolved to infect specific animal species, which means that a significant barrier exists that prevents animal pathogens from causing disease in humans. However, a portion of these pathogens, including influenza viruses and coronaviruses, have the capacity to evolve such that they can overcome these barriers and be successful, especially as there is no prior immunity in the human population.
This extraordinary ability to evolve also means that these pathogens have the potential to overcome vaccines. The application of vaccines and vaccine technology must progress to meet the challenge of zoonotic viruses.

Vaccine variety:
An impressive diversity of vaccine technologies is currently employed or in development to combat pathogens circulating in humans and animals. A vaccine needs to be effective at eliminating or reducing disease, but the diversity of pathogens means vaccines sometimes need to be equally diverse and must cater to specific challenges.

Traditional inactivated pathogen vaccines are generated by 'killing' a pathogen so that it can be safely administered for immunisation. Subunit vaccines are vaccines that comprise only a fragment of the target pathogen which can be administered to generate an immune response exclusively to that fragment.

Both technologies elicit protective antibody responses and have been successful for an exceptionally long time against a variety of pathogens. However, an antibody response does not provide sufficient protection against all pathogens that continually change their shapes to evade vaccines.

Live attenuated vaccines typically use infectious pathogens that are modified to prevent them from causing disease but can still trigger an immune response similar to their naturally occurring counterparts. These vaccines are useful because as well as an antibody response, they can induce a cellular immune response, which targets conserved parts of the pathogens that remain the same across different strains. This means live attenuated vaccines are more effective at protecting against mutations that could allow the pathogen to escape vaccine immunity and they provide better protection against multiple pathogen strains.

New vaccine technology:
Viral vector vaccines are vaccines that comprise the 'backbone' of a virus that doesn't cause disease in the host animal, which expresses a piece of the target pathogen that induces an immune response. Most licensed viral vector vaccines are in use in animals, with only a single vectored vaccine (against the Ebola virus) being licensed for humans prior to the SARS-CoV-2 pandemic.

Viral vector vaccines evoke a strong immune response that is specific to the pathogen, making it effective and long-lasting.

DNA/RNA vaccines contain genetic material that codes for a piece of a pathogen, which the host cells process to elicit an immune response. Several mRNA vaccines are in use against SARS-CoV-2 and they are cost-effective, safe, and produced using chemicals synthetically and not from cell culture systems.

As such, we now have the capacity to carefully select the target of our vaccines and the nature of the desired immune response. The importance of vaccines was brought into focus once again with the SARS-CoV-2 pandemic - and, going forward, the need for our growing arsenal of vaccines will only increase with the needs of humanity.

Nutrition:
As the human population increases so do its need for nutrition. A major source of human nutrition is animal-derived; thus, the population of farmed animals increases.

Wild habitats are encroached upon to provide for the increasing population of farmed animals, and this facilitates interaction between farmed and wild animals. Consequently, we develop a tractable route for zoonotic diseases to enter the human population.

Finally, the need for human nutrition is also met through the acquisition of wild animals. There is evidence to suggest that the West African Ebola virus epidemic was preceded by the capture of wild animals for human consumption. Likewise, SARS-CoV-2 is believed to have originated in wild animals.

Zoonotic diseases clearly have far-reaching impacts. Humans and animals directly suffer pathogen-related sickness and death, and global economies incur significant losses.

The current SARS-CoV-2 pandemic is a clear example of this - while avian influenza and several other emerging and re-emerging viruses carrying zoonotic infection potential circulating in farmed and wild birds are a constant reminder that the next pandemic could be around the corner.

Written by Professor Munir Iqbal and Dr Joshua Sealy, members of the Avian Influenza Virus group at Pirbright.
Year(s) Of Engagement Activity 2021
URL https://www.pirbright.ac.uk/news/2021/07/why-vaccines-matter-fight-against-zoonotic-diseases
 
Description Zoonotic Pathogens and Biorisk Management. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Talk was presented at workshop "Zoonotic Pathogens and Biorisk Management" at University of Veterianry and Animal Scieences Lahore, Pakistan and Institute of public health, Lahore 26-28 October 2016.

Both Medical and Veterinary professionals attended the workshop for CPD.
Year(s) Of Engagement Activity 2016