Combination Adjuvants and Conserved Antigen Provide Heterosubtypic Protection against Lethal Influenza Infection

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B194
Abstract ID: 5624

Presenting Author:
Ethan P. Laferriere , Graduate Student at Trudeau Inst., Clarkson Univ.

Abstract:

Influenza A virus (IAV) undergoes antigenic shift and drift, resulting in a wide variety of different coat proteins. These variations necessitate the reformulation of IAV vaccines to fight seasonal and pandemic strains. The use of pattern recognition receptors (PRR) agonists may enhance protection against IAV strains that differ in the outer coat proteins. We investigate if TLR4 (LPS) and TLR3 (poly IC) agonists in combination with conserved antigen, nucleoprotein (NP), from H3N2 virus can provide protection against lethal mismatched IAV challenge. Mice given NP with LPS + pIC in a prime/boost strategy demonstrate 80% survival after heterosubtypic challenge while H3 + NP in PBS showed 20% survival. Importantly, LPS + poly IC without protein antigen does not enhance survival. High endpoint titers of anti-NP antibodies cross react with H1N1 virus, suggesting a role for non-neutralizing antibodies in promoting survival. Further, LPS and pIC increased migratory monocyte DC in the lymph node in vivo, coupled with early upregulation of T cell marker CD69 when administered intramuscularly. In addition, Intranasal administration of LPS and pIC with NP induced high peptide specific IFN-gamma production in CD4 T cells and > 90% survival indicate a role for T cells and mucosal immunity. This combination strategy may provide increased efficacy over current IAV vaccines by inducing non-neutralizing antibodies and enhance T cell responses to conserved antigens.