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Title: Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine
Authors: 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
Keywords: Biochemistry, Genetics and Molecular Biology;Chemistry
Issue Date: 1-Dec-2019
Citation: Nature Communications. Vol.10, No.1 (2019)
Abstract: © 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.
ISSN: 20411723
Appears in Collections:Scopus 2019

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