HSV-2 antigens formulated with Matrix M-2 induce balanced neutralizing antibody and durable polyfunctional T cell responses in mice (113.5)

Abstract An effective HSV-2 vaccine is still needed despite the prevalence of antiviral drugs. Recent HSV-2 vaccine clinical trials highlighted the need to elicit potent T cell responses since neutralizing antibodies alone were incapable of providing complete protection. Through proteomic screens using T cells of HSV-2-exposed donors several antigens were identified as promising vaccine targets. Two of these antigens, GB208 and GB217 (GEN-003), were formulated with a saponin-derived adjuvant Matrix M-2, which in recent avian influenza human clinical trials induced cellular and humoral immune responses. In preclinical studies, C57BL/6 mice were used to evaluate the ability of GEN-003 combined with Matrix M-2 to induce antigen-specific T cell and antibody responses. T cell effector functions were evaluated by IFNγ ELISPOT, intracellular cytokine staining, and in vivo cytolysis of fluorescently labeled peptide-pulsed targets. Neutralizing antibody responses as well as total and subclass IgG titers were also assessed. Cellular and humoral immune responses were primed in mice after administering a wide range of protein and adjuvant doses. GB208- and GB217- specific T cell responses were polyfunctional, cytolytic, and persisted for more than 3 months. Antibody responses were neutralizing, and represented balanced Th1/Th2 phenotypes. In conclusion, GEN-003 combined with Matrix M-2 form a promising vaccine candidate that activates both arms of the immune system necessary for viral clearance.