Engagement of monocytes, NK cells, and CD4+ Th1 cells by ALVAC-SIV vaccination results in a decreased risk of SIVmac251 vaginal acquisition

Abstract

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 mac251. 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 mac251 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, α 4 β 7 + 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 CD4

Evolution and Diversity of Immune Responses during Acute HIV Infection

“…Moreover, changes in myeloid subsets during other acute viral infections are increasingly being shown to be associated with disease outcomes (Arts et al, 2018;Heung and Hohl, 2019;Kwissa et al, 2014;Michlmayr et al, 2020). Vaccine studies demonstrating protection conferred by NK cells and ILCs (Gorini et al, 2020;Rahman et al, 2019) suggest that these cells likely play more direct antiviral roles in controlling infection spread after onset of plasma viremia than is currently understood. Critically, how the timing and the magnitude of the initial innate responses to HIV infection impact the development of productive T and B cell responses has yet to be adequately explored.…”

Innate cell markers that predict anti-HIV neutralizing antibody titers in vaccinated macaques

“… 40 Also, NHP studies based on the ALVAC-SIV have associated monocytes signatures with a decreased risk of SIVmac251 acquisition. 27 , 41 In our manuscript, we also highlighted an important role of monocytes following the different vaccines including CD16 + non-classical and intermediate monocytes, especially for animals immunized with the HIV glycoprotein in MPLA adjuvant and by IM route. Furthermore, we also evidenced a role for CD11c + -CD16 + DCs that was not mentioned in these previous studies.…”

Innate Cell Markers That Predict Anti-HIV Neutralizing Antibody Titers in Vaccinated Macaques

“…40 Also, NHP studies based on the ALVAC-SIV have associated monocytes signatures with a decreased risk of SIV-mac251 acquisition. 27,41 In our manuscript, we also highlighted an important role of monocytes following the different vaccines including CD16 + non-classical and intermediate monocytes, especially for animals immunized with the HIV glycoprotein in MPLA adjuvant and by IM route. Furthermore, we also evidenced a role for CD11c + -CD16 + DCs that was not mentioned in these previous studies.…”