Engagement of monocytes, NK cells, and CD4 Th1 cells by ALVAC-SIV vaccination results in a decreased risk of SIV vaginal acquisition

The recombinant Canarypox ALVAC-HIV/gp120/alum vaccine regimen was the first to significantly decrease the risk of HIV acquisition in humans, with equal effectiveness in both males and females. Similarly, an equivalent SIV-based ALVAC vaccine regimen decreased the risk of virus acquisition in Indian rhesus macaques of both sexes following intrarectal exposure to low doses of SIV. Here, we demonstrate that the ALVAC-SIV/gp120/ alum vaccine is also efficacious in female Chinese rhesus macaques following intravaginal exposure to low doses of SIV and we confirm that CD14 classical monocytes are a strong correlate of decreased risk of virus acquisition. Furthermore, we demonstrate that the frequency of CD14 cells and/or their gene expression correlates with blood Type 1 CD4 T helper cells, αβ plasmablasts, and vaginal cytocidal NKG2A cells. To better understand the correlate of protection, we contrasted the ALVAC-SIV vaccine with a NYVAC-based SIV/gp120 regimen that used the identical immunogen. We found that NYVAC-SIV induced higher immune activation via CD4Ki67CD38 and CD4Ki67αβ T cells, higher SIV envelope-specific IFN-γ producing cells, equivalent ADCC, and did not decrease the risk of SIV acquisition. Using the systems biology approach, we demonstrate that specific expression profiles of plasmablasts, NKG2A cells, and monocytes elicited by the ALVAC-based regimen correlated with decreased risk of virus acquisition.