Browsing by Author "Rafick Pierre Sékaly"

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    Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine
    (2019-12-01) 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; International Vaccine Institute, Seoul; Thailand Ministry of Public Health; Walter Reed Army Institute of Research; Mahidol University; National Institutes of Health, Bethesda; Royal Thai Army; Duke University School of Medicine; Fred Hutchinson Cancer Research Center; Case Western Reserve University; Canadian Center for Computational Genomics
    © 2019, The Author(s). 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.