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Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine
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Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine
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Journal Article
Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine
2019
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/1
/ 38/61
/ Antigen Presentation - genetics
/ Antigen Presentation - immunology
/ Blood
/ Condoms
/ env Gene Products, Human Immunodeficiency Virus - immunology
/ Genes
/ HIV
/ HIV Infections - prevention & control
/ Human immunodeficiency virus
/ Humanities and Social Sciences
/ Humans
/ Immunoglobulin A - immunology
/ Immunoglobulin G - immunology
/ Interferon regulatory factor 7
/ Interferon Regulatory Factor-7 - metabolism
/ Interferon Type I - immunology
/ Interferon-gamma - immunology
/ Mechanistic Target of Rapamycin Complex 1 - genetics
/ Mechanistic Target of Rapamycin Complex 1 - metabolism
/ Placebos - administration & dosage
/ Risk
/ Science
/ Vaccines
