Award details

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

Reference	BB/R012679/1
Principal Investigator / Supervisor	Professor Munir Iqbal
Co-Investigators / Co-Supervisors	Dr John McCauley, Professor Richard Reeve
Institution	The Pirbright Institute
Department	Avian Influenza
Funding type	Research
Value (£)	506,107
Status	Completed
Type	Research Grant
Start date	01/01/2018
End date	30/06/2021
Duration	42 months

Abstract

unavailable

Summary

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.

Impact Summary

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-binding 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.

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	Animal Health, Immunology, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	Newton Fund - UK-China-Philippines-Thailand Swine and Poultry Research Initiative [2017]
Funding Scheme	X – not Funded via a specific Funding Scheme

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