HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes is associated with a decreased risk of SIVmac251 acquisition

Monica Vaccari, Slim Fourati, Shari N. Gordon, Dallas R. Brown, Massimilano Bissa, Luca Schifanella, Isabela Silva De Castro, Melvin N. Doster, Veronica Galli, Maria Omsland, Dai Fujikawa, Giacomo Gorini, Namal P.M. Liyanage, Hung V. Trinh, Katherine M. McKinnon, Kathryn E. Foulds, Brandon F. Keele, Mario Roederer, Richard A. Koup, Xiaoying ShenGeorgia D. Tomaras, Marcus P. Wong, Karissa J. Munoz, Johannes S. Gach, Donald N. Forthal, David C. Montefiori, David J. Venzon, Barbara K. Felber, Margherita Rosati, George N. Pavlakis, Mangala Rao, Rafick Pierre Sekaly, Genoveffa Franchini

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Qualitative differences in the innate and adaptive responses elicited by different HIV vaccine candidates have not been thoroughly investigated. We tested the ability of the Aventis Pasteur live recombinant canarypox vector (ALVAC)-SIV, DNA-SIV and Ad26-SIV vaccine prime modalities together with two ALVAC-SIV + gp120 protein boosts to reduce the risk of SIVmac251 acquisition in rhesus macaques. We found that the DNA and ALVAC prime regimens were effective, but the Ad26 prime was not. The activation of hypoxia and the inflammasome in CD14+CD16- monocytes, gut-homing CCR5-negative CD4+ T helper 2 (TH2) cells and antibodies to variable region 2 correlated with a decreased risk of SIVmac251 acquisition. By contrast, signal transducer and activator of transcription 3 activation in CD16+ monocytes was associated with an increased risk of virus acquisition. The Ad26 prime regimen induced the accumulation of CX3CR1+CD163+ macrophages in lymph nodes and of long-lasting CD4+ TH17 cells in the gut and lungs. Our data indicate that the selective engagement of monocyte subsets following a vaccine prime influences long-term immunity, uncovering an unexpected association of CD14+ innate monocytes with a reduced risk of SIVmac251 acquisition.

Original languageEnglish (US)
Pages (from-to)847-856
Number of pages10
JournalNature Medicine
Volume24
Issue number6
DOIs
StatePublished - Jun 1 2018
Externally publishedYes

Bibliographical note

Funding Information:
We thank D. Ahern for editorial and graphical support and all of the staff at Advanced BioScience Laboratories for helping with the execution of the animal study. We thank J. Lucas, J. Peel and Y. Lin for specific binding and total antibody assays and G. Overman and N. Yates for assay and technical assistance. We thank D. Barouch (Harvard Medical School) for providing the Ad26-SIV recombinant vaccine. This work was mostly supported with federal funds from the intramural program of the National Cancer Institute, NIH, including contract no. HHSN261200800001E (G.F.). Contributions were made by the extramural NIAID program (HHSN27201100016C; D.M.), the Henry M. Jackson Foundation, the US Department of Defense and the Collaboration for Aids Vaccine Discovery (CAVD) grants OPP1032325 (R.A.K.) and OPP1147555 (R.A.K.) from the Bill and Melinda Gates Foundation. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government.

Funding Information:
We thank D. Ahern for editorial and graphical support and all of the staff at Advanced BioScience Laboratories for helping with the execution of the animal study. We thank J. Lucas, J. Peel and Y. Lin for specific binding and total antibody assays and G. Overman and N. Yates for assay and technical assistance. We thank D. Barouch (Harvard Medical School) for providing the Ad26–SIV recombinant vaccine. This work was mostly supported with federal funds from the intramural program of the National Cancer Institute, NIH, including contract no. HHSN261200800001E (G.F.). Contributions were made by the extramural NIAID program (HHSN27201100016C; D.M.), the Henry M. Jackson Foundation, the US Department of Defense and the Collaboration for Aids Vaccine Discovery (CAVD) grants OPP1032325 (R.A.K.) and OPP1147555 (R.A.K.) from the Bill and Melinda Gates Foundation. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government.

Publisher Copyright:
© 2018 The Author(s).

Fingerprint

Dive into the research topics of 'HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes is associated with a decreased risk of SIVmac251 acquisition'. Together they form a unique fingerprint.

Cite this