Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine.
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.
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; Sékaly, R-P
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