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

Nature Communications
Slim FouratiRafick-Pierre Sékaly

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.

References

Aug 10, 2000·Scandinavian Journal of Immunology·H K MacHullaJ Langner
May 27, 2003·Nature Reviews. Immunology·Judy Lieberman
Dec 21, 2004·Molecular Immunology·Mark J SmythYoshihiro Hayakawa
May 12, 2005·Current Opinion in Immunology·Tatiana LebedevaYuri Sykulev
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Jan 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·Atsushi OkumuraPaula M Pitha
Feb 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yan ZhengJonathan D Powell
Feb 6, 2008·PLoS Pathogens·Pradeep D UchilWalther Mothes
Dec 3, 2008·The Journal of Experimental Medicine·Denis GaucherRafick-Pierre Sékaly
Oct 22, 2009·The New England Journal of Medicine·Supachai Rerks-NgarmUNKNOWN MOPH-TAVEG Investigators
Jul 9, 2011·Nature Immunology·Bali Pulendran, Rafi Ahmed
Jul 12, 2011·Nature Immunology·Helder I NakayaBali Pulendran
Feb 14, 2012·Current Opinion in Virology·John W Schoggins, Charles M Rice
Mar 23, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Stanley A Plotkin, Peter B Gilbert
Apr 6, 2012·The New England Journal of Medicine·Barton F HaynesJerome H Kim
May 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Georgia D TomarasBarton F Haynes
Jul 5, 2013·Bioinformatics·Renaud Gaujoux, Cathal Seoighe
Mar 25, 2014·Annual Review of Immunology·Daniel E ZakAlan Aderem
Jun 19, 2014·Bioinformatics·Hoifung PoonDavid Heckerman
Nov 8, 2014·Nucleic Acids Research·Danso Ako-AdjeiKim D Pruitt
Dec 30, 2014·Science Translational Medicine·Joan B MannickLloyd B Klickstein
May 26, 2015·Nature Biotechnology·Lin LinRaphael Gottardo
Jul 17, 2015·Science Translational Medicine·Heather A PrenticeRasmi Thomas
Oct 9, 2015·Journal of Virology·Matthew D J DicksMichael H Malim
Dec 15, 2015·Nucleic Acids Research·Antonio FabregatPeter D'Eustachio
Jan 16, 2016·Cell Systems·Arthur LiberzonPablo Tamayo
Apr 18, 2016·Cell·Dan H BarouchRafick-Pierre Sekaly
Jun 21, 2016·Current Protocols in Bioinformatics·Gil StelzerDoron Lancet
Dec 16, 2016·Cell Host & Microbe·Emilie BesnardEric Verdin
Nov 4, 2017·PLoS Computational Biology·Florian RohartKim-Anh Lê Cao

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Citations

Apr 30, 2019·Current Opinion in HIV and AIDS·Srivamshi PittalaMargaret E Ackerman
Aug 30, 2019·Science Translational Medicine·Philip K EhrenbergRasmi Thomas
Jul 21, 2020·Archiv der Pharmazie·Elida C G da MataElisabeth F Schwartz
Jul 7, 2020·Frontiers in Microbiology·Sergey IvanovOlga Tarasova
Sep 26, 2020·Science·Bali Pulendran, Mark M Davis
Feb 23, 2020·Molecular Cell·David E GordonNevan J Krogan
Aug 14, 2021·PLoS Pathogens·Michael J CorleyUNKNOWN SEARCH010/RV254 and SEARCH013/RV304 study groups
Nov 23, 2021·Journal of the International AIDS Society·Jiae KimJulie A Ake

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Methods Mentioned

BETA
transfection
flow cytometry
Electrophoresis
chips
FACS

Software Mentioned

Genecards
R package stats
Literome
HOMER
R package mixOmics
GeneRIF
GSEA
Reactome
FlowJo
MasterPlex

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