A-112 DNA and Protein Co-immunization Improves the Magnitude, Longevity, and mucosal dissemination of Immune Responses

Abstract

Background: To increase effectiveness of DNA vaccines, we developed a method of simultaneous vaccination of DNA and protein. DNA & protein (inactivated viral particles) co-immunization induced both systemic and mucosal Ab responses, which correlated with slower virus acquisition; and potent T cell responses, which correlated with protection from chronic viremia. Different regimens of DNA & protein vaccines using purified SIV/HIV-1 Env were evaluated to further improve mucosal dissemination. Methods: Macaques were vaccinated with SIV/HIV DNAs via the IM route using in vivo electroporation followed by protein administered into the same muscle. Immune responses were monitored in blood and mucosal sites including vaginal and rectal secretions. Results: DNA & protein co-immunization induced rapid and high humoral responses while maintaining robust cellular responses typically obtained with DNA. We found high systemic and mucosal antibody binding titers against gp120 as well as scaffolded V1/V2 env region; high levels of Env-specific IgG in saliva; Env-specific IgG and IgA in rectal mucosa; robust humoral responses in vaginal and rectal secretions. Importantly, while IM administered DNA vaccine induced cellular responses disseminated to mucosal sites, we noted poor dissemination of the humoral responses. In contrast, co-immunization with Env led to the significant increases in mucosal Ab dissemination. Co-immunization also resulted in improved longevity of immune responses detectable for several years. Conclusions: Intramuscular DNA & protein co-delivery increases the magnitude and longevity of systemic and mucosal humoral immune responses in immunized macaques and is proposed as a practical and efficient method for human vaccination.