CpG immunization protects against a lethal influenza challenge and generates antigen specific memory T cells (VAC2P.932)

Abstract

Abstract Despite extensive research, influenza A virus (IAV) remains a major cause of mortality and healthcare expenditure. Emerging pandemics from highly pathogenic IAV strains such as H5N1 and H1N1 highlight the need for universal, cross protective IAV vaccines. Current vaccine formulations generate strain-specific neutralizing antibodies primarily against the outer coat proteins hemagglutinin and neuraminidase. In contrast to these highly mutable proteins, internal proteins of IAV are more conserved and are therefore a favorable target for developing vaccines that induce strong T cell responses in the absence of humoral immunity. Here, we found that intranasal administration of a TLR 9 agonist (CpG) and inactivated x31 (H3N2) protects mice from a heterosubtypic challenge with a lethal dose of PR8 virus (H1N1). Vaccinated mice also showed less weight loss and lower viral titers compared to control mice following a lethal PR8 challenge. Both CD4 and CD8 effector functions were measured five days post challenge with significant increases in the number of Granzyme B positive cells as well as antigen specific IFN-γ cells. Additionally, vaccinated mice had higher memory recall responses following ex vivo restimulation with NP specific peptides as measured by IL-2 and IFN-γ production. Thus, CpG is a potent inducer of antiviral immunity highlighted by robust T cell responses underscoring the potential of this vaccination strategy as a prophylactic measure against pandemic IAV strains.