TY - JOUR
T1 - Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine
AU - Fourati, Slim
AU - Ribeiro, Susan Pereira
AU - Blasco Tavares Pereira Lopes, Filipa
AU - Talla, Aarthi
AU - Lefebvre, Francois
AU - Cameron, Mark
AU - Kaewkungwal, J.
AU - Pitisuttithum, P.
AU - Nitayaphan, S.
AU - Rerks-Ngarm, S.
AU - Kim, Jerome H.
AU - Thomas, Rasmi
AU - Gilbert, Peter B.
AU - Tomaras, Georgia D.
AU - Koup, Richard A.
AU - Michael, Nelson L.
AU - McElrath, M. Juliana
AU - Gottardo, Raphael
AU - Sékaly, Rafick Pierre
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85061820667
U2 - 10.1038/s41467-019-08854-2
DO - 10.1038/s41467-019-08854-2
M3 - Article
C2 - 30787294
AN - SCOPUS:85061820667
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 863
ER -