Early protection against pathogenic virus infection at a mucosal challenge site after vaccination with attenuated simian immunodeficiency virus.

Atraumatic application of attenuated SIVmac239 Delta nef vaccine to the tonsils of rhesus macaques provided protection against challenge 26 weeks later with infectious SIVmac251 applied through this route. Early events at the mucosal portal of entry of challenge virus were followed. Wild-type virus was detected in nonvaccinated controls by day 4, and then simian immunodeficiency virus (SIV) replicated vigorously at days 7 and 14. In contrast, a challenge of 10 of 10 vaccinees with SIV did not significantly raise RNA levels in the plasma or increase infected cells in lymphoid tissues, as assessed by single-cell labeling for viral RNA and nef protein. Vaccine virus was found in the tonsils of all vaccinees, but challenge virus was only detected at this portal of entry in 4 of 10 monkeys. In the tonsil, the challenge virus did not induce an expansion of perforin(+) killer cells. However, there was a significant increase in gamma delta T cells and mature dendritic cells relative to unvaccinated controls. Therefore, during tonsillar SIV Delta nef vaccination, infection is blocked early at the entry portal, which we propose is due in part to innate functions of gamma delta T and dendritic cells.