Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine

Slim Fourati, Susan Pereira Ribeiro, Filipa Blasco Tavares Pereira Lopes, Aarthi Talla, Francois Lefebvre, Mark Cameron, J. Kaewkungwal, P. Pitisuttithum, S. Nitayaphan, S. Rerks-Ngarm, Jerome H. Kim, Rasmi Thomas, Peter B. Gilbert, Georgia D. Tomaras, Richard A. Koup, Nelson L. Michael, M. Juliana McElrath, Raphael Gottardo, Rafick Pierre Sékaly*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The RV144 vaccine trial showed reduced risk of HIV-1 acquisition by 31.2%, although mechanisms that led to protection remain poorly understood. Here we identify transcriptional correlates for reduced HIV-1 acquisition after vaccination. We assess the transcriptomic profile of blood collected from 223 participants and 40 placebo recipients. Pathway-level analysis of HIV-1 negative vaccinees reveals that type I interferons that activate the IRF7 antiviral program and type II interferon-stimulated genes implicated in antigen-presentation are both associated with a reduced risk of HIV-1 acquisition. In contrast, genes upstream and downstream of NF-κB, mTORC1 and host genes required for viral infection are associated with an increased risk of HIV-1 acquisition among vaccinees and placebo recipients, defining a vaccine independent association with HIV-1 acquisition. Our transcriptomic analysis of RV144 trial samples identifies IRF7 as a mediator of protection and the activation of mTORC1 as a correlate of the risk of HIV-1 acquisition.

Original languageEnglish
Article number863
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2019
Externally publishedYes

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