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

Author

Listed:
  • Slim Fourati

    (Case Western Reserve University)

  • Susan Pereira Ribeiro

    (Case Western Reserve University)

  • Filipa Blasco Tavares Pereira Lopes

    (Case Western Reserve University)

  • Aarthi Talla

    (Case Western Reserve University)

  • Francois Lefebvre

    (Canadian Center for Computational Genomics)

  • Mark Cameron

    (Case Western Reserve University)

  • J. Kaewkungwal

    (Mahidol University)

  • P. Pitisuttithum

    (Mahidol University)

  • S. Nitayaphan

    (Armed Forces Research Institute of Medical Sciences)

  • S. Rerks-Ngarm

    (Ministry of Public Health)

  • Jerome H. Kim

    (Walter Reed Army Institute of Research
    International Vaccine Institute)

  • Rasmi Thomas

    (Walter Reed Army Institute of Research)

  • Peter B. Gilbert

    (Fred Hutchinson Cancer Research Center)

  • Georgia D. Tomaras

    (Duke University)

  • Richard A. Koup

    (US National Institutes of Health)

  • Nelson L. Michael

    (Walter Reed Army Institute of Research)

  • M. Juliana McElrath

    (Fred Hutchinson Cancer Research Center)

  • Raphael Gottardo

    (Fred Hutchinson Cancer Research Center)

  • Rafick-Pierre Sékaly

    (Case Western Reserve University)

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.

Suggested Citation

  • 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 & Jero, 2019. "Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08854-2
    DOI: 10.1038/s41467-019-08854-2
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