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 - Funding Information:
We would like to thanks Petra Stafova for performing the gene-expression arrays experiments; Nicole Frahm and Stephen De Rosa for providing us with the intracellular and Luminex data; Barton Haynes for comments on the protocol and the paper. This work made use of the High-Performance Computing Resource in the Core Facility for Advanced Research Computing at Case Western Reserve University. Grants from the Bill and Melinda Gates Foundation (OPP1032325 and OPP1147555) supported this work. S.F. received a travel fellowship from the Bill and Melinda Gates Foundation (OPP1084285).
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 - http://www.scopus.com/inward/record.url?scp=85061820667&partnerID=8YFLogxK
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 -