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- Title
Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine.
- Authors
Fourati, Slim; Ribeiro, Susan Pereira; Blasco Tavares Pereira Lopes, Filipa; Talla, Aarthi; Lefebvre, Francois; Cameron, Mark; Kaewkungwal, J.; Pitisuttithum, P.; Nitayaphan, S.; Rerks-Ngarm, S.; Kim, Jerome H.; Thomas, Rasmi; Gilbert, Peter B.; Tomaras, Georgia D.; Koup, Richard A.; Michael, Nelson L.; McElrath, M. Juliana; Gottardo, Raphael; Sékaly, Rafick-Pierre
- 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. The RV144 vaccine trial showed reduced risk of HIV-1 acquisition, but mechanisms underlying protection are poorly understood. Here, Fourati et al. assess the transcriptomic profile of blood collected from 223 vaccinees and 40 placebo recipients and identify IRF7 as a mediator of protection.
- Publication
Nature Communications, 2019, Vol 10, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-08854-2