Nat Commun. 2019 Feb 20; 10(1):863.

PubMed ID: 30787294

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

Fourati S, Ribeiro SP, Blasco Tavares Pereira Lopes F, Talla A, Lefebvre F, Cameron M, Kaewkungwal J, Pitisuttithum P, Nitayaphan S, Rerks-Ngarm S, Kim JH, Thomas R, Gilbert PB, Tomaras GD, Koup RA, Michael NL, McElrath MJ, Gottardo R, Sekaly RP

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.