Comparative analysis of SIV-specific cellular immune responses induced by different vaccine platforms in rhesus macaques

•Cellular immune responses induced by five SIV vaccine regimens in macaques•Identification of promising vaccine candidates for combination strategies•Systemic cellular immune responses capable of disseminating to mucosal sites•Presence of vaccine-induced T cells in vaginal mucosa•Likely contribution to containment of HIV/SIV at the portal of entry

To identify the most promising vaccine candidates for combinatorial strategies, we compared five SIV vaccine platforms including recombinant canary pox virus ALVAC, replication-competent adenovirus type 5 host range mutant RepAd, DNA, modified vaccinia Ankara (MVA), peptides and protein in distinct combinations. Three regimens used viral vectors (prime or boost) and two regimens used plasmid DNA. Analysis at necropsy showed that the DNA-based vaccine regimens elicited significantly higher cellular responses against Gag and Env than any of the other vaccine platforms. The T cell responses induced by most vaccine regimens disseminated systemically into secondary lymphoid tissues (lymph nodes, spleen) and effector anatomical sites (including liver, vaginal tissue), indicative of their role in viral containment at the portal of entry. The cellular and reported humoral immune response data suggest that combination of DNA and viral vectors elicits a balanced immunity with strong and durable responses able to disseminate into relevant mucosal sites.