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

This project will examine how vaccination strategies can affect pathogen evolution and transmission dynamics using mass vaccination of poultry in the face of avian influenza as a model system. Viral pathogens face the challenge of having to replicate and transmit within host populations that have immunity developed through prior infections or, in some cases, vaccination. Understanding how viruses respond to this challenge gives insight into how best to design and implement vaccination strategies. Some viruses, including influenza viruses, have developed the ability to rapidly evolve their targets of host immunity as a means to overcome the problem. This evolution in the face of host immunity is unpredictable and superficially understood. The research will include a combination of laboratory and mathematical approaches to explore the interplay between influenza virus evolution and vaccination done by a team of international researchers in the United States, the United Kingdom, and China. This research will provide training of graduate students and post-doctoral scholars, and important insights for policymakers in the fields of avian health, public health, and veterinary management. The recent emergence of clade 2.3.4.4 A(H5N1) influenza viruses across Asia, Africa, Europe, North America, and South America is unprecedented in terms of the scope of hosts and countries impacted. Birds that carry virus-neutralizing antibodies induced through vaccination or natural exposure are believed to be the key drivers of avian influenza virus evolution. The investigators propose to elucidate the repercussions of vaccine-driven evolutionary changes of A(H5N1) viruses to encompass virus epidemiology, antigenic landscape, transmission dynamics, host-range and pathogenesis. The main objectives will: (1) measure the antigenic diversity of recent A(H5) viruses, (2) identify A(H5) viruses evolved from vaccine protection, and (3) assess the transmission, host-range, and pathogenesis of the evolved A(H5) viruses. The combined data will be translated into mathematical models to predict viral emergence and transmission dynamics. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.