Understanding antigenic diversity, zoonotic potential and immunological prevention of avian influenza viruses affecting poultry

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

Abstract

Increasing poultry production is crucial for maintaining food supplies to feed the ever-increasing human population, and to meet the Sustainable Development Goal on food security and sustainable agriculture. However, emergence, re-emergence, and continued prevalence of avian influenza viruses (AIVs) in recent years threaten the sustainable growth of the poultry sector. Control of AIVs in areas of hyper-endemicity is primarily achieved through vaccination. However, effectiveness of most conventional poultry vaccines is intrinsically sub-optimal; these vaccines generally only mask clinical signs and mortality, while still allowing infected animals to shed infectious viruses. Existing vaccines may consequently result in continued circulation and evolution of AIVs, and improved vaccines are therefore required that produce robust, sterile immunity against clinical disease and silent transmission, thus breaking the endemic cycle within farming systems.

The proposed research aims to gain insight into viral factors that contribute to vaccine failure which may enhance the ability of AIVs to cross species barriers from birds to mammals. We will utilise next-generation vaccination technologies and develop robust and effective vaccines that elicit strong and durable humoral and cellular immune responses against AIVs that cause severe economic losses in poultry. Our specific objectives are to investigate: (i) what changes in contemporary AIV of H5 and H7 subtypes infecting poultry can be implicated in vaccine failure, or are critical for inducing protective immunity in vaccinated birds; (ii) how do molecular changes in the virus surface increase the ability of the virus to transmit from poultry to humans; (iii) the delivery of protective antigens to chicken immune cells to potentiate more robust protection against AIV.

Achieving these objectives will provide unique data sets enabling: (i) selection of vaccine strains that match with the field viruses to provide greater protection in vaccinated birds; (ii) assessment of the likelihood of increased zoonotic infection risks to humans from the currently circulating AIV viruses in China; (iii) development of novel vaccine technologies that utilises attenuated live viruses as vaccine delivery vectors, such as recombinant herpesvirus of turkey (HVT). The efficient production and controlled delivery of protective AIV antigens to immune cells will drive induction of rapid, strong and life-long humoral and cellular immunity in chickens.

The ready availability of better disease control tools will aid in the reduction of poultry production losses and thus be important for global food security and improved animal welfare, whilst also reducing possible zoonotic transmission to humans. Thus, the proposed research partnership will provide direct benefits to farming communities and substantial indirect economic, public health, environmental and social benefits on a global scale.

Planned Impact

The proposed research will develop new knowledge and tools for combating H5 and H7 avian influenza virus (AIV) infections in poultry, thus minimising their zoonotic transmission to humans. The negative consequences of animal pathogens on trade restrictions, food security, public health, and the livelihood and quality of life of millions of farming and farming-associated communities around the world is evident globally. This is exemplified from the recent outbreak of H5N8 and H7N7 high pathogenicity avian influenza in the UK in 2015/2016, in which only a handful of localised farm outbreaks led to the culling of over one million high-value units of poultry. Furthermore, a 10-kilometre restriction zone was implemented around the infected premises where domestic poultry and mammals were not allowed to be moved, resulting in further economic losses to neighbouring farms. Considering these scenarios, any further spread of AIV could incur severe losses to the UK poultry industry, which accounts for approximately £8 billion in the UK economy and supports over 80,000 jobs. An even higher level of devastation to poultry production is being caused by both H5 and H7 viruses in China, as well as many other countries around the world. Additionally, zoonotic infections in humans have resulted in over 450 deaths from H5N1 globally since 2003, and over 600 deaths from H7N9 mainly in China since 2013. Minimising the impact of these viruses in poultry, with the concomitant reduction in zoonotic transmission, requires the improved knowledge of their genetic and antigenic diversity that this project will provide, enabling development of more effective control measures including new and improved vaccination technologies. Such steps will particularly help reduce the prevalence of AIVs in China, where the disease is endemic in poultry.

Our proposed research will provide integrated and innovative approaches to the prevention and control of AIV by demonstrating antigenic and receptor-bindng properties of contemporary field viruses which inflict economic losses in poultry and cause zoonotic infections in humans. The specific outcome of this research will allow vaccine seed strain selection that induces cross-protective immunity against emergent field variants. Novel vaccine technologies that deliver protective antigens directly to immune cells through attenuated live virus vectored vaccines will induce strong cellular and humoral immunity. This immunity should overcome the sub-optimal performance and other inherent drawbacks of currently available conventional killed virus vaccines. This research will therefore be of value to many stakeholders involved in animal and public health and in food security.

The research impacts will be enhanced by prompt publishing of the outcomes via peer-reviewed, open-access journals, as well as regular presentations at conferences and workshops. Proactive engagements will be undertaken with potential stakeholders with interest in improving livestock disease control and prevention strategies, including funding bodies and policy makers in UK (BBSRC, MRC, Defra), China (NSFC), partner institutions, and international organizations (World Organization for Animal Health (OIE), Food and Agriculture Organization of the United Nations (FAO), World Health Organization (WHO). To achieve these goals all PIs, researchers and collaborators involved in the project will use every available opportunity to disseminate the research to relevant stakeholders for the wider public benefit.

Publications

10 25 50
 
Description The research developed in vitro-based virus-immune escape assays that imitate natural virus evolution within vaccinated animals. This in vitro antiserum escape mutant selection method proved very powerful tool to predict the antigenic change of influenza viruses, also replacing the animal use for these studies
Exploitation Route Selection of vaccine seed viruses for production of more effective vaccines against avian influenza viruses.
Sectors Agriculture, Food and Drink,Communities and Social Services/Policy,Creative Economy,Education,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description The research defined underlying mechanism how natural infection and vaccine induced immunity drive avian influenza H7N9 avian infleunza viruses to evolve and persists in poultry. The research outcomes will help for selection of future vaccine development and seed strain assessment by providing quantitative molecular markers that can help explain vaccine breakdown in the field and predict levels of antigenic drift during virus surveillance.
First Year Of Impact 2018
Sector Agriculture, Food and Drink,Communities and Social Services/Policy,Creative Economy,Education,Environment,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
 
Description BBSRC-iCASE
Amount £100,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2019 
End 09/2023
 
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 04/2019 
End 03/2024
 
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. 
 
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 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 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 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 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 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 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 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 Influenza update meeting (Pengxiang Chang) 
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 presented work entitled: Antigenic characterization of avian influenza H7N9 virus by in vitro immune escape mutant selection method.
Year(s) Of Engagement Activity 2018
 
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 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 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 UK-China Philippines-Thailand Swine and Poultry Research Initiative project kick-off workshop 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research update meeting for Principal investigators and researchers involved in "UK-China Philippines-Thailand Swine and Poultry Research Initiative project".75 researchers and representative from funding bodies from UK, China, Philippines-Thailand also attended the meeting.
Year(s) Of Engagement Activity 2018
 
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/