Location: Virus and Prion Research
Project Number: 5030-32000-109-02-R
Project Type: Reimbursable Cooperative Agreement
Start Date: May 1, 2013
End Date: Dec 31, 2014
Current vaccines used to control swine influenza A virus (SIV) include inactivated products delivered by intramuscular administration. While these types of vaccines induce a peripheral antibody response that allows serum antibody to be used in a hemagglutination inhibition (HI) assay to evaluate functional antibody to SIV antigen, next generation IAV vaccines, particularly intranasally delivered products, typically do not induce a robust serum antibody response. However, these vaccine platforms have been shown to be highly efficacious, even when delivered in the face of maternal antibody. Thus, if these newer vaccine platforms are going to be used, better antemortem assays are needed for evaluating vaccination status, evaluating cross-reactivity to drifted viruses, and ultimately, predicting cross-protection. The purpose of this proposal is to explore several different assays to identify at least one that could be used at the diagnostic level to predict protection/cross-protection to field viruses following intranasal vaccination with different next generation swine IAV vaccines.
Initially, we will test several different assays that evaluate cell-mediated immune responses, specifically interferon-gamma production in a recall assay by ELISA and ELISpot, using peripheral blood mononuclear cells or whole blood. We will also evaluate mucosal antibody in both nasal wash and oral fluids in a neutralization assay and whole-virus ELISA. We propose these types of assays because previous work indicates that intranasal SIV vaccines induce a strong cell-mediated immune response as well as antibody at the mucosa, as opposed to peripheral antibody in the sera. In addition, these sample types (peripheral blood, nasal wash and/or oral fluids) would be easy to collect and therefore producers would be more amenable to their collection. In addition, diagnostic labs already handle these specimen types. Initially pigs will be vaccinated by the intranasal route with either a live-attenuated IAV or replication-defective adenovirus encoding IAV HA and used for repeated sampling (blood, nasal wash and oral fluids). Once the assays have been established a subsequent study will be performed in which vaccinated pigs are challenged with heterologous virus to evaluate cross-protection and how protection correlates to responses detected in each assay.