Location: Virus and Prion Research
Project Number: 5030-32000-231-105-R
Project Type: Reimbursable Cooperative Agreement
Start Date: Jun 7, 2023
End Date: Jun 7, 2025
Objective:
reduce influenza A virus (IAV) levels in swine populations to reduce the probability of human spillover events
Approach:
Aim 1: Development of multivalent mRNA-LNP vaccines that elicit broad neutralizing antibodies against emerging swine subtypes (i.e. multivalent vaccine targeting multiple H1 & H3 strains). The cooperator PI recently demonstrated that mRNA-LNPs can be used to elicit immune responses against 20 different HA subtypes simultaneously. This type of vaccine is useful to prime immunity against all potential pandemic influenza virus strains, but it is not a vaccine that is expected to elicit neutralizing antibodies against every specific influenza virus strain that has pandemic potential. In this Aim, the cooperator will create multivalent mRNA-LNP vaccines that express up to 20 HA immunogens from a single subtype. ARS will work closely with the cooperator team to select immunogens that represent all major clades within each subtype for rational design targeting swine IAV. The overall goal of this project is to create subtype-specific multivalent vaccines that elicit neutralizing antibodies against multiple clades of viruses within single subtypes simultaneously. Cooperator will first complete immunogenicity and challenge studies in mice and ferrets. ARS will then test immunogenicity in pigs and conduct Aim 2 to test these vaccines in swine.
Aim 2: Testing of multivalent mRNA-LNP vaccines in swine. We will test vaccines developed by the cooperator in ARS swine vaccination and challenge model with strains relevant to swine and human health. For swine studies, vaccinated animals will be challenged via an intranasal + intratracheal route with homologous or heterologous virus. Blood will be collected from multiple timepoints pre- and post-vaccination. Pigs will be humanely euthanized on days 5 and/or 21 days post inoculation (dpi) to evaluate protection from challenge as well as mucosal and peripheral immune responses. Immune parameters against the vaccine and challenge strains will be evaluated, Host immune response will also be evaluated by histologic techniques.
