US-UK-China Collab: Understanding the Impact of Poultry Vaccination on H5Nx Avian Influenza Virus Evolution and Ecosystem Dynamics

Avian influenza virus (AIV) infection is a major global disease that continues to threaten wildlife, poultry production and public health. The A/goose/Guangdong/1/1996 (H5N1) lineage of Highly pathogenic avian influenza (HPAI) H5 viruses remains epizootic worldwide. The recent emergence of clade 2.3.4.4 HPAI H5Nx viruses have spread across Asia, Europe, North America, South America, and Africa in unprecedented numbers. The H5Nx viruses pose great challenges to domestic poultry industry and wild birds. AIVs undergo adaptation through the interaction with host immune systems. Birds that carry virus-neutralizing antibodies induced through vaccination or natural exposure are believed to be the key drivers of the AIV evolution. Through the immunological pressure imposed by the neutralizing antibodies, AIVs evolve to evade host immune defenses. The dynamic process of adaptation and counter-adaptation is a driving force of the AIV evolution. This proposed research will aim to address the evolution of HPAI H5 viruses with the impact of vaccination to improve disease control systems against H5Nx HPAIVs by defining how viruses cause disease and continue to circulate in poultry. Additionally, determining the effects of infections with HPAIV on morbidity, mortality, and transmission, and ultimately will provide insight into virus evolution and ecology for mitigation approach development (vaccines and antivirals) to help reduce production losses and zoonotic or pandemic threats from the viruses. We aim to elucidate the repercussions of the evolutionary change of the viruses to encompass virus epidemiology, antigenic landscape, transmission dynamics, host-range and pathogenesis. We have proposed to work as a collaborative consortium, harnessing the combined expertise of six research organizations across the United States, the United Kingdom and China. This proposed project is structured into six work packages, each with its specific objectives. The main objectives will cover the following: i). Defining the antigenic diversity of the H5Nx viruses. ii). Identification of the H5Nx viruses that will evolve from vaccine protection through in vivo and deep mutational scanning approaches. iii). Assessment of the transmission, host-range and pathogenesis of the evolved H5Nx viruses in avian and mammalian models. These data will be translated into iv) Mathematical models to predict the emergence and transmission dynamics of the evolved H5Nx viruses. Altogether, this research will advance our understanding of H5Nx HPAIV evolution under the influence of vaccination and provide important insights for policymakers in the fields of avian health, public health, and veterinary management. The evolved strains are detrimental to poultry and also lead to zoonotic infections. Our proposed research will be beneficial for researchers across various disciplines, including influenza virology, epidemiology, virus evolution, and virus control in humans and animals. This study will provide crucial insights into the potential risks from emerging AIVs, thereby benefiting individuals involved in disease surveillance and control. Our prescriptive risk prediction will benefit a broad range of stakeholders by enabling effective mitigation strategies and reducing disease burden. This will result in lessened disease control costs, positively impacting public health, the economy, and the environment. This project will foster US-UK-China research collaboration to address AIV evolution and the threats posed by emerging and re-emerging AIV variants to public and animal health. This provides a unique opportunity for the establishment of research partnerships, and the data and reagents generated through this project will be shared across the globe and will benefit enormously in the international scientific community in human and livestock health.