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

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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.