Highly Immunogenic JVRS-100 Adjuvanted Universal Influenza A Vaccine (52.4)

Abstract

Abstract A vaccine based on a conserved external ectodomain of M2 (M2e) offers the potential for inducing broad-immunity against divergent influenza A strains including pandemic viruses. Cohorts of mice were vaccinated 3x (IM) with M2e in the form of a multiple antigenic peptide with 4 copies of M2e (MAP4), with or without cationic lipid DNA complex adjuvant (JVRS-100). Lethal challenge using different strains of virus (H1N1, H3N2) were done to establish efficacy based on survival. The addition of JVRS-100 to M2e-MAP4 resulted in a significant decrease in morbidity and mortality following lethal challenge with H1N1 (survival 100% vs. 30% without adjuvant) or H3N2 (80% vs. 20%). Adjuvanted vaccine resulted in higher levels of IgG (p=0.0159), IgG1 (p<0.02) and IgG2a (p<0.005) vs. M2e-MAP4 alone. A dose titration of M2e-MAP4 inoculated with a constant amount of JVRS-100 resulted in 100% survival after challenge even at a vaccine dose of 25ng. Addition of M2e-MAP4/JVRS-100 to trivalent inactivated influenza vaccine (TIV) confers full protection with a single vaccination prior to lethal challenge. Competitive binding ELISA confirmed that the sera from vaccinated mice contained M2e conformational epitopes. Vaccination with MAP2 and MAP4 indicated the protective epitopes were dependent on dimeric and not tetrameric configuration of the MAP construct. The experiments demonstrate the potency of MAP configured M2e peptide with the JVRS-100 adjuvant in the development of universal flu vaccine.