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

Publication ,  Journal Article
Fourati, S; Ribeiro, SP; Blasco Tavares Pereira Lopes, F; Talla, A; Lefebvre, F; Cameron, M; Kaewkungwal, J; Pitisuttithum, P; Nitayaphan, S ...
Published in: Nat Commun
February 20, 2019

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

February 20, 2019

Volume

10

Issue

1

Start / End Page

863

Location

England

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Placebos
  • NF-kappa B
  • Mechanistic Target of Rapamycin Complex 1
  • Interferon-gamma
  • Interferon Type I
  • Interferon Regulatory Factor-7
  • Immunoglobulin G
  • Immunoglobulin A
  • Immunization
 

Citation

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Fourati, S., Ribeiro, S. P., Blasco Tavares Pereira Lopes, F., Talla, A., Lefebvre, F., Cameron, M., … Sékaly, R.-P. (2019). Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine. Nat Commun, 10(1), 863. https://doi.org/10.1038/s41467-019-08854-2
Fourati, Slim, Susan Pereira Ribeiro, Filipa Blasco Tavares Pereira Lopes, Aarthi Talla, Francois Lefebvre, Mark Cameron, J. Kaewkungwal, et al. “Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine.Nat Commun 10, no. 1 (February 20, 2019): 863. https://doi.org/10.1038/s41467-019-08854-2.
Fourati S, Ribeiro SP, Blasco Tavares Pereira Lopes F, Talla A, Lefebvre F, Cameron M, et al. Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine. Nat Commun. 2019 Feb 20;10(1):863.
Fourati, Slim, et al. “Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine.Nat Commun, vol. 10, no. 1, Feb. 2019, p. 863. Pubmed, doi:10.1038/s41467-019-08854-2.
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 R-P. Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine. Nat Commun. 2019 Feb 20;10(1):863.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

February 20, 2019

Volume

10

Issue

1

Start / End Page

863

Location

England

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Placebos
  • NF-kappa B
  • Mechanistic Target of Rapamycin Complex 1
  • Interferon-gamma
  • Interferon Type I
  • Interferon Regulatory Factor-7
  • Immunoglobulin G
  • Immunoglobulin A
  • Immunization