A minimalist, self-adjuvanting vaccine achieves robust immune response to conserved influenza peptide M2e 3184

Abstract Description Adjuvants specifically targeting innate immune receptors such as toll-like receptors (TLRs) offer an attractive, precise approach for enhancing immune responses for peptide and protein vaccines. Covalent attachment of TLR agonists can elicit increased proinflammatory cytokine production, dendritic cell activation, and priming of cellular and humoral immune responses. Here, we utilized a TLR2 agonist, Pam3CysSK4G (Pam), chemically conjugated to a helper CD4+ epitope (IAd) and the well-defined influenza A virus M2e ectodomain (M2e) peptide to create a minimalist, self-adjuvanting vaccine (Pam-IAd-M2e). M2e is an exemplary antigen for defining the immune potentiating effects of this vaccine platform because it is well-described as an influenza antigen, capable of eliciting non-neutralizing antibodies and protective CD4+ responses; however, it is poorly immunogenic on its own, enabling demonstration of the potency of conjugated TLR adjuvanting. To display proof of concept, we first employed in vitro assays to show significantly increased cytokine production and antigen uptake compared to M2e alone. We then demonstrated significantly increased antibody titers in vivo from Pam-IAd-M2e immunization compared to M2e alone, as well as employed orthogonal assays to elucidate antigen-specific CD4+ T-cell characteristics. These promising results indicates this vaccine platform is capable of targeting specific immunostimulatory pathways and eliciting immunity to concise pathogen epitopes. Topic Categories Vaccines and Immunotherapy (VAC)