|Author||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|
|Title||Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine.|
|Journal Name||Nat Commun|
|Month / Year||08/2019|
|Vol (No)||10 (1)|
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-kappaB, 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.
|Keyword||AIDS Vaccines/*immunology; Antigen Presentation/genetics/immunology; HIV Antibodies/immunology; HIV Infections/immunology/*prevention & control; HIV-1/*immunology; Humans; Immunization; Immunoglobulin A/blood/immunology; Immunoglobulin G/blood/immunology; Interferon Regulatory Factor-7/*metabolism; Interferon Type I/*immunology; Interferon-gamma/*immunology; Mechanistic Target of Rapamycin Complex 1/genetics/*metabolism; NF-kappa B/metabolism; Placebos/administration & dosage; env Gene Products, Human Immunodeficiency Virus/immunology|