Location: Virus and Prion Research
Project Number: 5030-32000-231-025-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Sep 1, 2019
End Date: Aug 31, 2022
Objective:
Objective 1: Define the molecular basis for evolution of hemagglutinin (HA) and neuraminidase (NA) proteins in circulating swine influenza A virus (IAV).
Objective 2: Generate and test alternative influenza A virus (IAV) vaccine platforms against swine IAV.
Approach:
Site-directed mutagenesis and reverse engineering will be used to generate viruses with newly identified HA antigenic motifs and to construct relevant NA neuraminidase inhibition assay antigens. These HA mutants and NA reassortants will be evaluated in serologic assays combined with antigenic cartography. A live-attenuated influenza virus (LAIV) vaccine containing an attenuated (att) swine-origin backbone was developed and shown to be safe, cross-protective against challenge with antigenically distinct viruses in pigs and significantly more efficacious than inactivated vaccines. Alternative approaches will be developed to improve the breadth of the response of this LAIV technology, as well as new alternative vaccine technologies to generate safe and more broadly cross-protective IAV vaccine for pigs. The new vaccines will be tested in vitro for their growth characteristics and stability. The safety, immunogenicity and protection against IAV infection will be assessed in swine by ARS.
