Intradermal but not intramuscular MVA immunizations protect against intravaginal tier2 SHIV challenges in macaques

Route of immunization can markedly influence the quality of immune response. Here, we show that intradermal (ID) but not intramuscular (IM) modified vaccinia Ankara (MVA) vaccinations provide protection from acquisition of intravaginal tier2 SHIV challenges in female macaques. Both routes of vaccination induced comparable levels of serum IgG with neutralizing and non-neutralizing activities. The protection in MVA-ID group correlated positively with serum neutralizing and antibody-dependent phagocytic activities, and envelope-specific vaginal IgA; while the limited protection in MVA-IM group correlated only with serum neutralizing activity. MVA-ID immunizations induced greater germinal center Tfh and B cell responses, reduced the ratio of Th1 to Tfh cells in blood and showed lower activation of intermediate monocytes and inflammasome compared to MVA-IM immunizations. This lower innate activation correlated negatively with induction of Tfh responses. These data demonstrate that the MVA-ID vaccinations protect against intravaginal SHIV challenges by modulating the innate and T helper responses. We vaccinated two groups of rhesus macaques with 10 animals per group using the DNA/MVA/Protein vaccine regimen. Animals in both groups were primed with DNA/SHIV-BG505-CD40L via the ID route and electroporation at weeks 0 and 8. At weeks 16 and 24, all animals were boosted with MVA/SHIV-BG505 delivered through either ID or IM routes.