Location: Virus and Prion Research
Project Number: 5030-32000-231-085-R
Project Type: Reimbursable Cooperative Agreement
Start Date: Apr 1, 2021
End Date: Mar 31, 2025
Objective:
Objective 1: Quantify USA swine influenza A virus genetic and antigenic evolution via passive and active surveillance.
Objective 2: Determine global genetic and antigenic relationships of swine and human IAV.
Objective 3: Determine the risks associated with human-swine interspecies transmission to address pandemic preparedness.
Objective 4: Investigate pathogenesis and transmission of emerging influenza A viruses in swine and ferret hosts to address pandemic preparedness.
Objective 5: Evaluate post-infection and post-vaccine immune responses in pigs and the consequence of sequential exposure to influenza A viruses.
Approach:
This work will build on a foundation of H1, H3, and N2 swine serum panels generated at ARS and ferret serum panels shared by collaborators. The previous panels will be used to measure ongoing evolution of contemporary swine IAV isolates and quantify genetic and antigenic divergence from current human seasonal IAV, candidate vaccine viruses used for pandemic preparedness, or swine IAV vaccine strains. Antisera panels, viruses, and sequences will be updated to determine antigenic relatedness between swine and human strains using swine and ferret antisera to identify highly divergent swine strains that are currently circulating regionally and globally. Influenza isolates with genetic or phenotypic properties of interest will be evaluated for pathogenesis and transmission in pigs and/or transmission between pigs and ferrets as a risk model for humans. In vivo pig studies will be conducted to determine the kinetics driving variable immune responses following exposure to H1 and H3 IAV subtypes (antigenic imprinting) in the swine host. The magnitude of interaction by sequential exposures of different subtypes and the immune mechanisms of antigenic imprinting will be assessed. Vaccine efficacy of different vaccine platforms in the face of prior immunity and antigenic imprinting can then be evaluated.
