CpG vaccination induces cytolytic T cells to the lung and heterosubtypic protection against lethal IAV infection (P4289)

Abstract

Abstract With the emergence of pandemic influenza A virus (IAV) strains such as H1N1 and H5N1, the development of a universal vaccine has become more necessary than ever. In contrast to the highly mutable outer coat proteins, internal proteins of IAV are more conserved among different strains and are therefore a target for developing vaccines that induce strong T cell responses. Using a Toll-like receptor 9 agonist with unmethylated CpG motifs, we have shown that intranasal immunization with CpG and inactivated x31 (H3N2) IAV protects mice following a heterosubtypic challenge with a lethal dose of PR8 virus (H1N1). Vaccination with CpG and inactivated IAV cause a stronger inflammatory response than IAV infection alone, with significant levels of antiviral cytokines such as MIP-1β, CXCL 10, and IL-6 produced in the lungs. Furthermore, CpG immunization induces a substantial influx of CD11b+ cells into the draining lymph nodes as well as a population of CD11c+ cells that express high levels of the costimulatory molecule CD86, providing favorable conditions for T cell activation. At 6 days post immunization, effector CD4 and CD8 T cells expressing Granzyme B and IFN-γ are observed in the lungs of vaccinated mice. These experiments suggest that TLR agonists can act as potent immune adjuvants to generate robust T cell immunity capable of combating IAV and other viral infections where successful vaccines have not yet been developed.