Comparative evaluation of prophylactic SIV vaccination modalities administered to the oral cavity.

Chaudhary, Omkar; Wang, Lingyun; Bose, Deepanwita; Narayan, Vivek; Yeh, Ming Te; Carville, Angela; Clements, John; Andino, Raul; Kozlowski, Pamela A; Aldovini, Anna

Attempts to develop a protective HIV vaccine have had limited success, especially in terms of inducing protective antibodies capable of neutralizing different viral strains. As HIV transmission occurs mainly via mucosal surfaces, HIV replicates significantly in the gastrointestinal tract, and the oral route of vaccination is a convenient one to implement worldwide, we explored three SIV vaccine modalities administered orally and composed of SIV DNA priming with different boosting immunogens, with the goal of evaluating whether they could provide lasting humoral and cellular responses, including at mucosal surfaces that are sites of HIV entry. Twenty-four Cynomolgus macaques (CyM), were primed with replication-incompetent SIV DNA provirus and divided into three groups for the following booster vaccinations, all administered in the oral cavity: Group 1 with recombinant SIV gp140 and E. coli heat-labile toxin adjuvant dmLT, Group 2 with recombinant SIV-Oral Poliovirus (SIV-OPV), and Group 3 with recombinant SIV-MVA. Cell-mediated responses were measured using blood, lymph node, rectal and vaginal mononuclear cells. Significant levels of systemic and mucosal T-cell responses against Gag and Env were observed in all groups. Some SIV-specific plasma IgG, rectal and salivary IgA antibodies were generated, mainly in animals that received SIV DNA + SIV-MVA, but no vaginal IgA was detected. Susceptibility to infection after SIVmac251 challenge was similar in vaccinated and non-vaccinated animals, but acute infection viremia levels were lower in the group that received SIV DNA + SIV-MVA. Non-vaccinated CyM macaques maintained central memory and total CD4+ T cell levels in the normal range during the 5 months of post-infection follow-up as did the vaccinated animals, precluding evaluation of vaccine impact on disease progression. We conclude that the oral cavity vaccination tested in these regimens can stimulate cell-mediated immunity systemically and mucosally, but humoral response stimulation was limited with the doses and the vaccine platforms used.