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 and Rafick-Pierre Sékaly ()
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Slim Fourati: Case Western Reserve University
Susan Pereira Ribeiro: Case Western Reserve University
Filipa Blasco Tavares Pereira Lopes: Case Western Reserve University
Aarthi Talla: Case Western Reserve University
Francois Lefebvre: Canadian Center for Computational Genomics
Mark Cameron: Case Western Reserve University
J. Kaewkungwal: Mahidol University
P. Pitisuttithum: Mahidol University
S. Nitayaphan: Armed Forces Research Institute of Medical Sciences
S. Rerks-Ngarm: Ministry of Public Health
Jerome H. Kim: Walter Reed Army Institute of Research
Rasmi Thomas: Walter Reed Army Institute of Research
Peter B. Gilbert: Fred Hutchinson Cancer Research Center
Georgia D. Tomaras: Duke University
Richard A. Koup: US National Institutes of Health
Nelson L. Michael: Walter Reed Army Institute of Research
M. Juliana McElrath: Fred Hutchinson Cancer Research Center
Raphael Gottardo: Fred Hutchinson Cancer Research Center
Rafick-Pierre Sékaly: Case Western Reserve University

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-08854-2

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