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

Giacomo Gorini, Slim Fourati, Monica Vaccari, Mohammad Arif Rahman, Shari N. Gordon, Dallas R. Brown, Lynn Law, Jean Chang, Richard Green, Fredrik Barrenäs, Namal P.M. Liyanage, Melvin N. Doster, Luca Schifanella, Massimiliano Bissa, Isabela Silva de Castro, Robyn Washington-Parks, Veronica Galli, Deborah H. Fuller, Sampa Santra, Michael AgyRanajit Pal, Robert E. Palermo, Georgia D. Tomaras, Xiaoying Shen, Celia C. LaBranche, David C. Montefiori, David J. Venzon, Hung V. Trinh, Mangala Rao, Michael Gale, Rafick P. Sekaly, Genoveffa Franchini

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 SIVmac251. 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 SIVmac251 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, α4β7 + 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+Ki67+CD38+ and CD4+Ki67+α4β7 + T cells, higher SIV envelope-specific IFN-γ producing cells, equivalent ADCC, and did not decrease the risk of SIVmac251 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.

Original languageEnglish (US)
Article numbere1008377
JournalPLoS pathogens
Volume16
Issue number3
DOIs
StatePublished - Jan 1 2020
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported with federal funds from the intramural program of the National Cancer Institute, National Institutes of Health, including Contract No. HHSN261200800001E to G. F. Contributions were made by the extramural NIAID program (HHSN27201100016C to N. Miller, HHSN2722013000021 to J. Warren, and HHSN272201300010C and HHSN272201800008C to M.G.), the Henry M. Jackson Foundation, the US Department of Defense, and the Collaboration for Aids Vaccine Discovery (CAVD) grants OPP1032325, OPP1032817, and OPP1147555 to M.R., from the Bill and Melinda Gates Foundation, and the Washington National Primate Research Center Office of the Director (P51OD010425) to L. L. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

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