Pirbright Institute Flexible Talent Mobility Account

Lead Research Organisation: The Pirbright Institute
Department Name: Administration Office

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Publications

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Clements AL (2021) PA-X is an avian virulence factor in H9N2 avian influenza virus. in The Journal of general virology

 
Description The award is still ongoing and has suffered some delays due to Covid-19, especially regarding international travel, a major requirement and output of the original award objectives. However, some Innovation Placements and Fellowships did go ahead, with some adjustments to allow for home working or amended timeframes where necessary.

Skills development
A young industrial researcher from Jordan gained experience at Pirbright to safely analyse the infectious pathogens and learn techniques for the improvement of vaccines against avian influenza viruses affecting poultry. Also increased biosecurity and biosafety knowledge for handling live virus.
An Innovation Fellow from Pirbright gained experience in an animal breeding company, including managing a small research project in a commercial setting and developed new research tools. The Fellow has since taken on a senior postdoctoral position at Pirbright, where she is responsible for the further development of research and training activities within the Institute's CL3 facilities.
An Innovation Fellow from Pirbright completed a placement at a UK company, where she gained skills and experience in test validation, kit manufacture, industrial scale up procedures, quality control, and general commercial and consumer awareness. The researcher has since gone on to a new position in the partner company.
Other Innovation Fellows from Pirbright undertook placement at UK companies involved in insecticide development and manufacturing, gene editing, and bioengineering in single- and multiorgan microphysiological systems. During these placements they learnt skills related to commercial manufacturing, quality control and market research.
An Innovation Fellow from Pirbright underwent specialist training in intellectual property (IP) management and a placement at an IP management company to gain experience in IP and market research. He wrote a white paper regarding trends in human and veterinary vaccine manufacturing and delivery systems.
An Innovation Placement within the Knowledge Exchange and Commercialisation (KEC) team allowed a PhD student to experience technology transfer and intellectual property management within the research sector. The student has since gone on to a permanent position within the KEC team.

Scientific findings include:
A new research method for the detection of avian leukosis virus.
Characterisation of a proprietary cell line to confirm its suitability for the propagation of multiple avian leukosis virus subtypes.
A Covid-19 loop-mediated isothermal amplification testing kit in partnership with a commercial kit manufacturer.
A trial to determine the effectiveness of multiple Covid-19 diagnostic assays leading to the ongoing use of the most reliable assays during the pandemic.
Establishment of an organ-on-chip system at Pirbright to study virus-host interactions for improving animal health linking it to the industrial challenge area of transforming food production. This also has the potential to reduce reliance on experimental animal models.
Exploitation Route Collaborations
Strengthening an existing relationship with JOVAC, a Jordanian animal vaccine manufacturer.
Strengthened a new relationship with a UK based animal breeding company. This relationship is likely to lead to multiple collaborative projects, including projects funded by the company and joint applications such as BBSRC Link awards.
Establishing a new relationship with a US based SME involved in establishing automated experimentation on small animal model organisms. This project is still ongoing.
Strengthening an existing relationship with a UK-based insecticide manufacturer.
Sectors Agriculture, Food and Drink,Chemicals,Environment,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description The award is still ongoing and we anticipate further outputs and impacts, especially regarding the international element of this award, which was significantly delayed due to Covid-19 travel restrictions. UK-based placements had to be adapted to allow for remote working and in some instance the objectives of the project were adjusted as original lab or field based work was no longer possible. Talent/skills In two cases, the placement of an individual in a setting outside of academic research has precipitated a career move of that individual to a different sector. At least one other individual has explicitly expressed an interest in making the move to industry in the near future. In this way, the award has had a societal and economic impact by directly enabling the transfer of talent between economic sectors. In another project, an individual based in a company abroad (Jordan) spent time in our laboratories, gaining skills and experience and transferring that knowledge back to his company. This individual has remained in contact with researchers at Pirbright and he is now using his new knowledge to support local technical representatives with technical information on vaccine efficacy. The availability of effective disease mitigation tools offers direct benefits to the livelihoods of poultry producers and also substantial indirect benefits to the wider communities linked to the poultry value chain that are severely impacted by the economics, public health, and environmental consequences of livestock disease. Other projects involved Pirbright's Innovation Fellows spending time with UK-based companies, where they gained new skills and experience in non-academic sector. This experience could lead to future collaborations with the companies and will support the Innovation Fellows in having a more holistic understanding of the role of research in the economy. Societal/economic impact The placement of an Innovation Fellow within a UK diagnostics company increased the UK's capacity for test provision during the Covid-19 outbreak. Policy Data from a study related to the effectiveness of Covid-19 diagnostic assays informed the UK government on the performance of such assays.
First Year Of Impact 2021
Sector Agriculture, Food and Drink,Environment,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description Protecting poultry from avian influenza, Newcastle disease, infectious bronchitis, and Gumboro disease with a single dose of a multivalent vaccine
Amount £448,937 (GBP)
Funding ID BB/W003325/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2022 
End 12/2023
 
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 Live virus titration - positive staining of ALV foci. 
Description The method is based on positive staining of ALV (Avian Leukosis Virus) antigen conserved among all virus subtypes and utilises a coloured enzymatic substrate to present virus-formed foci on cell monolayer. 
Type Of Material Technology assay or reagent 
Year Produced 2020 
Provided To Others? No  
Impact This method could be used to titrate live ALV present in tested samples or stocks, in contrast to widely employed ELISA-based titration, which relies on protein (viral antigen) quantification. The number of virus-formed foci directly represents the number of live infectious particles present in the titrated stock. Since ALV is a slow-growing virus, the virus-formed foci could be visualised earlier than the viral plaques developed as a result of cytopathic effect on cells, thus shortening the duration of assay by 2-3 days. 
 
Title Direct RNA sequencing of Deformed Wing Virus A in Ame711 honey bee cells 
Description PolyA mRNA was isolated from Ame711 honey bee cells and directly sequenced using a Flongle nanopore flow cell. The Ame711 cell line is infected with Deformed Wing Virus A at high levels. 
Type Of Material Data analysis technique 
Year Produced 2022 
Provided To Others? No  
Impact Data are still being analysed 
 
Title FDA drug screening of RSV and SARS-CoV-2 cell-cell fusion 
Description Using inducible cell-cell fusion assays for SARS-CoV-2 and RSV we have screened the FDA approved use drug library for inhibitors of these viral-induced processes 
Type Of Material Data analysis technique 
Year Produced 2022 
Provided To Others? No  
Impact No impact as yet, data still being validated in live virus assays 
 
Title Transcriptomic analysis of Deformed Wing Virus A infected primary honey bee cells with nanopore sequencing 
Description Primary cells were extracted from honey bee pupae and infected with DWVA. 8 days post-infection, cells were harvested, polyA mRNA purified, reverse transcribed and amplified by PCR. Uninfected and infected samples were barcoded, pooled and nanopore sequenced using a Minion flow cell. 
Type Of Material Data analysis technique 
Year Produced 2022 
Provided To Others? No  
Impact Data are still being analysed 
 
Description Assessment of E1E2 fusion activity of different HCV strains using a reporter cellular system 
Organisation University of Glasgow
Department MRC - University of Glasgow Centre for Virus Research
Country United Kingdom 
Sector Academic/University 
PI Contribution Technology transfer of the cellular split reporter system used by our group to assess fusion activity of viral glycoproteins
Collaborator Contribution Characterisation of HCV E1E2 using structural prediction (Alphafold), production of infectious viruses and experimentally determined intrinsic entropy of glycoproteins' domains.
Impact Submitted publication on BioRxiv: https://www.biorxiv.org/content/10.1101/2020.11.11.377218v2
Start Year 2021
 
Description Collaborative UK-based partnership for RT-LAMP assays 
Organisation Animal and Plant Health Agency
Country United Kingdom 
Sector Public 
PI Contribution During the secondment by EH, a small collaborative study was performed with Hampshire Hospitals NHS Foundation Trust (HHFT), the Animal and Plant Health Agency (APHA) and University of Southampton (UoS) to develop a new RT-LAMP methodology for COVID-19 testing.
Collaborator Contribution EH was asked to provide assistance to an existing project on RT-LAMP methodology. All parties were involved in methodological development, resulting in a collaborative paper being published.
Impact Collaborative publication including all partners was published in the Journal of Virological Methods.
Start Year 2020
 
Description Collaborative UK-based partnership for RT-LAMP assays 
Organisation Hampshire Hospitals NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution During the secondment by EH, a small collaborative study was performed with Hampshire Hospitals NHS Foundation Trust (HHFT), the Animal and Plant Health Agency (APHA) and University of Southampton (UoS) to develop a new RT-LAMP methodology for COVID-19 testing.
Collaborator Contribution EH was asked to provide assistance to an existing project on RT-LAMP methodology. All parties were involved in methodological development, resulting in a collaborative paper being published.
Impact Collaborative publication including all partners was published in the Journal of Virological Methods.
Start Year 2020
 
Description Collaborative UK-based partnership for RT-LAMP assays 
Organisation University of Southampton
Country United Kingdom 
Sector Academic/University 
PI Contribution During the secondment by EH, a small collaborative study was performed with Hampshire Hospitals NHS Foundation Trust (HHFT), the Animal and Plant Health Agency (APHA) and University of Southampton (UoS) to develop a new RT-LAMP methodology for COVID-19 testing.
Collaborator Contribution EH was asked to provide assistance to an existing project on RT-LAMP methodology. All parties were involved in methodological development, resulting in a collaborative paper being published.
Impact Collaborative publication including all partners was published in the Journal of Virological Methods.
Start Year 2020
 
Description Collaborative UK-based partnership for insect control commercial opportunties 
Organisation Vecotech Ltd
Country United Kingdom 
Sector Private 
PI Contribution Financial contributions towards FTMA placement which is intended for: Specialist mosquito repellent wristbands market analysis Alternative/additional market reports Database access to Statista, the foremost resource for market intelligence statistics providing essential statistics Vecotech staff time for training and onboarding the Innovation Fellow The purchase of competitor repellent device products for design and functionality assessments
Collaborator Contribution The contributions made by the partners include: Staff time towards supporting the Innovation Fellow in all project aspects Market research database reports worth at least £3500 Access to Vecotech's regulatory consultants for relevant advice
Impact Expanded the award holders professional network, the contacts gained could be useful for future relationships. Market research reports assessing the insect repellent market will be useful to both the partner and research team at the home Institute.
Start Year 2021
 
Description Collaborative partnership for establish of PhysioMimix™ OOC system 
Organisation CN Bio Innovations Ltd
Country United Kingdom 
Sector Private 
PI Contribution During the secondment by YZ, a small, independent experiment was performed with CN Bio Innovations Ltd using the PhysioMimix™ OOC system to culture HepG2 cells.
Collaborator Contribution CN Bio Innovations Limited provided training to one Pirbright scientist for 4 weeks at the CN-Bio laboratory at Cambridge Science Park, Cambridge. During the training, Pirbright scientist worked along with their team on ongoing projects in the experimental set up, familiarisation with the use of PhysioMimix™ instrument in various techniques including cell seeding for setting up OOC, evaluation of the results, and problem solving.
Impact PhysioMimix™ OOC system has been installed successfully and optimization of animal cells culture is performing.
Start Year 2020
 
Description Direct RNA sequencing of replicating Deformed Wing Virus, a major pathogen of honey bees 
Organisation Fera Science Limited
Country United Kingdom 
Sector Public 
PI Contribution I produced in vitro RNA derived from a clone of deformed wing virus, harvested cells from an immortalised honey bee cell line (Ame711) and harvested deformed wing infected primary honey bee cells. These materials were brought to Fera Science Ltd in order to carry out direct RNA nanopore sequencing on deformed wing virus and deformed wing virus infected honey bee cells. Whilst at Fera, I gave a practical demonstration on isolation of primary cells from honey bee pupae. We were able to successfully isolate primary honey bee cells and observe them under a microscope.
Collaborator Contribution Scientists at Fera shared their expertise of nanopore sequencing, guiding me during the sample preparation steps and performing some of the RNA extraction steps. Demonstrations of how to load samples into Flongle and Minion nanopore flow cells were provided and by the end of the project I was able to load flow cells myself. Bioinformatics support was provided to enable analysis and visualisation of direct RNA sequencing data.
Impact Knowledge exchange
Start Year 2022
 
Description Infecting Culicoides sonorensis with Leishmania parasites 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Country United Kingdom 
Sector Academic/University 
PI Contribution This research has allowed further incrimination of the vector species of Leishmania in Ghana, assisting with the identification of a novel pathogen-vector interaction. I have established a protocol for the testing of Culicoides biting midges at LSHTM for Leishmania, which was previously developed and optimised by colleagues in Ghana at the University of Cape Coast.
Collaborator Contribution LSHTM provided the use of CL2 laboratory facilities, including laboratory equipment and space in order to conduct DNA extraction and PCR analysis. Additionally, they have trained me on how to infect Culicoides sonorensis with Leishmania parasites.
Impact This collaboration has enabled stronger links between all parties working on Leishmania in the UK, bringing together expertise in Culicoides biting midges and Leishmania infection in sandflies. The outputs from the laboratory work complete the preliminary data required for an application for larger grant funding that will extend this collaboration into the future.
Start Year 2022
 
Description Partnership on the use of pigs as an animal model in biomedical research 
Organisation Technical University of Munich
Country Germany 
Sector Academic/University 
PI Contribution Training of postdoctoral fellow on the establishment of multicolor staining panels in flow cytometry for pigs, aiming at the identification of hematopoietic stem cells.
Collaborator Contribution Provision of sample material and in kind contribution of reagents.
Impact Training of postdoctoral fellow Establishment of new marker panel for identification of hematopoietic stem cells in pigs Multi-disciplinary collaboration between immunologists and geneticists.
Start Year 2022
 
Description Screening of FDA compounds on wild-type SARS2 or recombinant reporter viruses. 
Organisation University of Glasgow
Department MRC - University of Glasgow Centre for Virus Research
Country United Kingdom 
Sector Academic/University 
PI Contribution Screening of a FDA compound library using a cellular reporter system based on split eGFP and engineered to express SARS2 S protein to assess the efficiency of drugs to viral fusion inhibition.
Collaborator Contribution Validation of identified active compounds against SARS2 fusion activity using wild-type virus or its VOCs.
Impact No outcome yet.
Start Year 2022
 
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: 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 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 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 Improvement in the Production Systems and Potency of Poultry Vaccines. Virtual meeting organised by Hi-Tech Poultry Breeders (Pvt) Ltd, Lahore, Pakistan. 17th January 2022 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact A talk entitled "Improvement in the Production Systems and Potency of Poultry Vaccines" was presented by Munir Iqbal to veterinary field staff working on poultry production, particularly prevention and control of infectious diseases. The Audience was very much impressed with the new improved technology that enhance the potency of poultry vaccines.
Year(s) Of Engagement Activity 2022
 
Description Improving Poultry Vaccines, Virtual presentation to staff and postgraduate students at University of Veterinary and Animal Sciences, Lahore, Pakistan 
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 The overview was presented on the development of next-generation of poultry vaccines. The new vaccine technology selectively targets chicken immune cells and induces faster and stronger immunity against poultry viral diseases. A huge interest in the subject was perceived and everyone was interested in the new technology and eager in suggesting that this vaccine should be taken forward for commercial production and field use.
Year(s) Of Engagement Activity 2022
 
Description Microphysiological Systems for Human Preclinical Drug Research, 23rd Nov 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Presentation title: Microphysiological Systems for Human Preclinical Drug Research, Audrey Dubourg (Product Manager, OOC, CN-Bio) and her colleague Atefeh Mobasseri (Field Application specialist from CN-Bio) visited The Pirbright Institute and gave a talk on 'Microphysiological Systems for Human Preclinical Drug Research' followed by a discussion. Audrey also gave a demonstration of the PhysioMimix OOC system.
Year(s) Of Engagement Activity 2021
 
Description PhysioMimix™ cell culture technology 
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 After four weeks of intensive training, Dr Yaoyao Zhang departed CN Bio Innovations, a Cambridge-based bioengineering company, ready to incorporate new technology and skills into her own research at The Pirbright Institute. The Pirbright Institute and CN Bio Innovations posted the news on Tweet, Facebook and LinkedIn. The researchers are very interested to use this new technology to explore animal research.
Year(s) Of Engagement Activity 2020
URL https://www.pirbright.ac.uk/news/2020/11/science-spotlight-bringing-home-new-technologies
 
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 Pirbright's new bird flu vaccine provides rapid protection, could reduce virus spread and is less costly to produce 
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 online at the Pirbright Institute webpage and One Health Poultry Health webpage and distributed wildly on social media including Facebook, Twitter, In Share. Our research outputs were mass comminated for the general public.
An improved poultry influenza vaccine has been developed by researchers from The Pirbright Institute. The potential vaccine triggers a rapid immune response which 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.

Many poultry flu vaccines protect birds from serious illness and death, but do not prevent them from transmitting the virus. In recent years, new methods have been developed to enhance the immune responses that vaccines produce and reduce the amount of virus shed by birds into the environment.

One of these techniques involves tagging flu virus proteins with a marker that makes them easier for Antigen Presenting Cells (APCs) to capture. These immune cells can efficiently process the tagged proteins resulting in robust and long-lasting antiviral responses in chickens.

For the first time, researchers at Pirbright have shown that tagging the flu virus haemagglutinin (HA) protein and directing it to target a specific protein on the chicken APCs, called CD83, generates faster and stronger immune responses against the H9N2 bird flu strain compared to the current industry standard inactivated virus vaccine.

The results published in npj Vaccines revealed that the vaccine was both fast-acting and effective. Birds produced antibody responses as early as six days after vaccination and they shed significantly less flu virus when challenged with a natural flu strain, indicating the birds would be less likely to spread infection. High levels of protective antibodies were produced even when birds were given a reduced dose.

As well as providing enhanced protection, this vaccine will be easier and less costly to manufacture. The tagged flu virus HA protein can be produced in a laboratory culture of insect cells instead of using eggs to grow live vaccine viruses. This would enable the poultry industry to reduce its reliance on chicken eggs for vaccine production, increasing the availability of eggs for use as a food source. The use of laboratory cells instead of eggs also highlights how Pirbright scientists actively develop animal health solutions that apply the principles of the 3Rs (Reduce, Refine, Replace) in animal research.

As the new vaccine does not contain live flu virus, biosafety risks are reduced and no specialist high containment facilities would be required for production. These qualities make the vaccine very attractive for large scale manufacture. The Pirbright team is currently investigating the vaccine's potential for commercial production and use in the field.

Professor Munir Iqbal, Head of Pirbright's Avian Influenza Virus group, said: "By targeting HA to chicken immune cells, we have generated a powerful addition to the armoury of poultry vaccines. Our improved vaccine could help prevent the spread of flu amongst vaccinated birds, which is essential for protecting poultry welfare, increasing food production, and reducing the risk of avian influenza spreading to humans."

This research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation (UKRI).
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 Poultry Vaccines Production approaches: Recombinant-HVT and subunit vaccines. Poultry stakeholders meeting with the field veterinarian. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact A Talk entitled "Poultry Vaccines Production approaches: Recombinant-HVT and subunit vaccines" was presented by Munir Iqbal to field veterinarian working on prevention and control of poultry diseases. This poultry stakeholders meeting was held in Cairo, Egypt on12th February 2022.
Year(s) Of Engagement Activity 2022
 
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 Product Launch 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Several press releases were published following the successful launch of a novel bed bug monitoring product developed by collaborating partner Vecotech.
These press releases were published from professional bodies (e.g. Pest Control News and BCPA), the associated research institute (LSHTM) and the funding body (UKRI)

Pest Control News - BugScents™ product launch - published 20th January 2021
https://www.pestcontrolnews.com/new-bed-bug-lure-from-vecotech/
UKRI news - BugScents™ product launch - published 25th January 2021
https://www.ukri.org/news/university-spin-out-battles-bed-bugs-with-pheromone-innovation/
LSHTM news - BugScents™ product launch - published 26th January 2021
https://www.lshtm.ac.uk/newsevents/news/2021/chemical-attraction-new-pheromone-based-bed-bug-lure-help-better-detect
BCPA Press release - BugScents™ product launch - published 29th January 2021
https://bpca.org.uk/News-and-Blog/Sector/vecotech-launches-novel-bed-bug-pheromone-based-lure-/267493
Year(s) Of Engagement Activity 2021
URL https://www.ukri.org/news/university-spin-out-battles-bed-bugs-with-pheromone-innovation/
 
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 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 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 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