OA24.04
Background: Determining the quality and longevity of vaccine-induced immune responses is essential for improving the prospects of AIDS vaccines. DNA and protein (inactivated viral particles) co-immunization regimen induced systemic and mucosal Ab responses, which correlated with slower virus acquisition upon challenge, and potent T cell responses providing protection against chronic viremia. We are evaluating different regimens of DNA&protein vaccines using purified SIV or HIV-1 Env to further dissect humoral and cellular responses including magnitude, breadth and mucosal dissemination.
Methods: Macaques were vaccinated using DNA&protein co-immunization regimen in the presence of IL-12 DNA, coinjected into the same muscle. Humoral and cellular responses were monitored in blood and different tissues.
Results: Co-immunization strategy of DNA&protein induced rapid and high humoral responses while maintaining robust cellular responses typically obtained with DNA vaccines. The vaccine induced Ab against both homologous and heterologous Env; high binding titers against scaffolded V1/V2 env region; efficient dissemination to mucosal sites; high Env-specific IgG in saliva and Env-specific IgG and IgA in rectal mucosa. Analysis of cellular responses revealed the presence of cytotoxic memory T cells against several viral proteins. These cellular responses disseminated systemically as demonstrated by their presence not only in blood and lymphoid tissues, but also in bone marrow, liver, lung (effector site) and, importantly, rectal and vaginal mucosa. The longevity of the cellular responses induced by this co-immunization regimen was significantly improved, with SIV-specific T cells detected>5 yrs after the vaccination.
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.
