Cationic Liposome-DNA Complex Adjuvant (JVRS-100) Combined with Heat-Inactivated Whole Virion Influenza Vaccine Confers Protection against Homotypic and Heterosubtypic Lethal Challenge (132.1)

Abstract

Abstract Background: Current vaccine strategies for influenza are highly dependent on matching of hemagglutinin, which is susceptible to periodic antigenic drift. A vaccine that elicits a robust antibody and T-cell response would be less susceptible to primary vaccine failure. Methods: Balb/c mice were vaccinated with heat-inactivated PR/8/34 (H1N1) or HKx31 (H3N2) with or without the JVRS-100 adjuvant. Mice were assessed for antibody and T-cell responses as well as challenged with a lethal dose of PR/8/34. Mice were monitored for clinical signs of infection, changes in body weight, and mortality. Results: Mice vaccinated with heat-inactivated virus combined with JVRS-100 adjuvant, showed increased HAI (450 vs. 30, P=0.007) and T-cell responses based on splenocyte restimulation (7700 vs. 30 pg/ml, P<0.001) when compared with unadjuvanted virus. Mice vaccinated with homologous virus with adjuvant exhibited no weight loss at six days post infection (+5.4% vs. -15.3%) compared with unadjuvanted virus following 6xLD50 challenge with PR/8/34. Mice vaccinated with JVRS-100-adjuvanted heterologous virus also showed less weight loss (-7% vs. -26.7%, P=0.004) compared with unadjuvanted virus following 6xLD50 challenge with PR/8/34. Conclusion: Heat-inactivated whole influenza virus adjuvanted with JVRS-100 showed increased immunogenicity and greater protection from homotypic and heterosubtypic lethal challenge. Adoptive transfer studies suggest that the cross-protection is due at least in part to a cross-reactive antibody response.