Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine

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

doi:10.1038/s41467-019-08854-2

Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine

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^*

^*Corresponding author for this work

Medicine, Allergy Division

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

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.

Original language	English (US)
Article number	863
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-08854-2
State	Published - Dec 1 2019

Funding

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).

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-019-08854-2

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Fourati, S., Ribeiro, S. P., Blasco Tavares Pereira Lopes, F., Talla, A., Lefebvre, F., Cameron, M., Kaewkungwal, J., Pitisuttithum, P., Nitayaphan, S., Rerks-Ngarm, S., Kim, J. H., Thomas, R., Gilbert, P. B., Tomaras, G. D., Koup, R. A., Michael, N. L., McElrath, M. J., Gottardo, R., & Sékaly, R. P. (2019). Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine. Nature communications, 10(1), Article 863. https://doi.org/10.1038/s41467-019-08854-2

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title = "Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine",

abstract = "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.",

author = "Slim Fourati and Ribeiro, {Susan Pereira} and {Blasco Tavares Pereira Lopes}, Filipa and Aarthi Talla and Francois Lefebvre and Mark Cameron and J. Kaewkungwal and P. Pitisuttithum and S. Nitayaphan and S. Rerks-Ngarm and Kim, {Jerome H.} and Rasmi Thomas and Gilbert, {Peter B.} and Tomaras, {Georgia D.} and Koup, {Richard A.} and Michael, {Nelson L.} and McElrath, {M. Juliana} and Raphael Gottardo and S{\'e}kaly, {Rafick Pierre}",

note = "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: {\textcopyright} 2019, The Author(s).",

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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 & Sékaly, RP 2019, 'Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine', Nature communications, vol. 10, no. 1, 863. https://doi.org/10.1038/s41467-019-08854-2

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AU - Ribeiro, Susan Pereira

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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

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Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine

Abstract

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ASJC Scopus subject areas

UN SDGs

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