Location: Virus and Prion Research
Project Number: 5030-32000-231-000-D
Project Type: In-House Appropriated
Start Date: Oct 5, 2021
End Date: Oct 4, 2026
Objective:
Objective 1. Characterize the ecology, epidemiology, and pathogenesis of emerging swine Influenza A viruses (IAVs) with a focus on the One-Health concept.
1.1. Characterize the pathogenesis, determine the course of infection and evaluate the virulence, focusing on the hemagglutinin, of new and emerging swine IAVs that have the potential to impact swine health and/or affect public health.
1.2. Conduct genetic and antigenic characterization of new and emerging swine IAVs, including phylogenetics and network analysis.
1.3. Identify the molecular mechanisms by which non-swine adapted viruses infect and adapt to swine.
1.4. Using computational methods, characterize new and emerging swine IAVs with regard to entire genetic background (HA, NA and other 7 genes), that have the potential to impact swine health and/or affect public health.
2. Develop intervention strategies to effectively control endemic swine IAVs, including new emerging strains associated with disease outbreaks.
2.1. Enhance virus control and recovery strategies by elucidating the environmental ecology of swine IAVs.
2.2. Characterize the effect of vaccine induced immunity on swine IAV evolution.
2.3. Evaluate and improve existing and new diagnostic tests and testing strategies for swine IAV surveillance, detection, and recovery from disease outbreaks.
2.4. Characterize swine innate and adaptive immune responses to swine IAVs and determine correlates of protection.
2.5. Investigate and develop new vaccine platforms that improve broad cross-protection, override interference from prior immunity, and rapidly control and respond to new and emerging IAV outbreaks in the various components of swine production.
Approach:
Influenza A virus (IAV) will be investigated in swine or relevant in vitro models to 1) understand the genetic predictors of host range and virulence in swine; 2) understand the genetic and antigenic variability of endemic viruses and how this affects vaccine strain selection and efficacy; and 3) develop new vaccines that can override maternally-derived antibody interference and provide broader cross-protection. Disease pathogenesis, transmission, and vaccine efficacy studies will be conducted in the natural swine host. Knowledge obtained will be applied to break the cycle of transmission through development of better vaccines or other novel intervention strategies. Computational biology methods will be used to evaluate virus evolution in the natural host to enable predictions to be made on virulence and/or antigenic factors. These predictions will be tested in the lab and in animal studies with wild type viruses and through the use of reverse engineering and mutational studies to identify virulence components of IAV. Experimentally mutated viruses will be evaluated by test parameters that measure both virus and host properties. Development of vaccines that provide better cross-protective immunity than what is currently available with today's vaccines will be approached through understanding correlates of protection, the impact of prior exposure or passive immunity, and through vaccine vector platform development, attenuated strains for vaccines, and other novel vaccine technologies.
