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

增加家禽生产对于维持粮食供应、养活不断增长的人口以及实现关于粮食安全和可持续农业的可持续发展目标至关重要。然而，近年来禽流感病毒(AIV)的出现、重新出现和持续流行威胁着家禽业的可持续增长。在高度流行地区控制AIV主要是通过接种疫苗实现的。然而，大多数传统家禽疫苗的效力本质上是次优的；这些疫苗通常只掩盖临床症状和死亡，同时仍允许受感染的动物传播传染性病毒。因此，现有疫苗可能导致AIV的持续传播和进化，因此需要改进的疫苗，以产生对临床疾病和沉默传播的强大、无菌免疫，从而打破农业系统内的地方性循环。这项拟议的研究旨在深入了解导致疫苗失败的病毒因素，这可能会增强AIV跨越从鸟类到哺乳动物的物种障碍的能力。我们将利用下一代疫苗接种技术，开发强大而有效的疫苗，对造成严重经济损失的禽流感病毒产生强大而持久的体液和细胞免疫反应。我们的具体目标是调查：(I)感染家禽的H5和H7亚型当代禽流感病毒的哪些变化可能与疫苗失败有关，或对诱导接种疫苗的禽类产生保护性免疫至关重要；(Ii)病毒表面的分子变化如何增加病毒从家禽传播到人类的能力；(Iii)将保护性抗原输送到鸡的免疫细胞，以加强对禽流感病毒的更强有力的保护。实现这些目标将提供独特的数据集，使：(I)选择与野外病毒匹配的疫苗毒株，以在接种疫苗的禽类中提供更大的保护；(Ii)评估中国目前流行的禽流感病毒对人类的人畜共患感染风险增加的可能性；(Iii)开发利用减毒活病毒作为疫苗递送载体的新型疫苗技术，如土耳其重组疱疹病毒。高效生产和可控制地将保护性AIV抗原输送到免疫细胞将推动对鸡快速、强大和终身的体液和细胞免疫的诱导。现成的更好的疾病控制工具将有助于减少家禽生产损失，因此对全球粮食安全和改善动物福利非常重要，同时还可以减少人畜共患传染病向人类传播的可能性。因此，拟议的研究伙伴关系将在全球范围内直接惠及农业社区，并带来可观的间接经济、公共卫生、环境和社会效益。

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.