Slim FouratiSusan Pereira RibeiroFilipa Blasco Tavares Pereira LopesAarthi TallaFrancois LefebvreMark CameronJ. KaewkungwalP. PitisuttithumS. NitayaphanS. Rerks-NgarmJerome H. KimRasmi ThomasPeter B. GilbertGeorgia D. TomarasRichard A. KoupNelson L. MichaelM. Juliana McElrathRaphael GottardoRafick Pierre SékalyInternational Vaccine Institute, SeoulThailand Ministry of Public HealthWalter Reed Army Institute of ResearchMahidol UniversityNational Institutes of Health, BethesdaRoyal Thai ArmyDuke University School of MedicineFred Hutchinson Cancer Research CenterCase Western Reserve UniversityCanadian Center for Computational Genomics2020-01-272020-01-272019-12-01Nature Communications. Vol.10, No.1 (2019)204117232-s2.0-85061820667https://repository.li.mahidol.ac.th/handle/20.500.14594/50023© 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryArticleSCOPUS10.1038/s41467-019-08854-2