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Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV

Author

Listed:
  • Mario Roederer

    (Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA)

  • Brandon F. Keele

    (SAIC-Frederick, Frederick National Laboratory, NIH, Frederick, Maryland 21702, USA)

  • Stephen D. Schmidt

    (Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA)

  • Rosemarie D. Mason

    (Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA)

  • Hugh C. Welles

    (Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
    George Washington University)

  • Will Fischer

    (Los Alamos National Laboratories)

  • Celia Labranche

    (Duke University)

  • Kathryn E. Foulds

    (Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA)

  • Mark K. Louder

    (Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA)

  • Zhi-Yong Yang

    (Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
    Present address: Sanofi-Pasteur, Cambridge, Massachusetts 02139, USA.)

  • John-Paul M. Todd

    (Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA)

  • Adam P. Buzby

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center)

  • Linh V. Mach

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center)

  • Ling Shen

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center)

  • Kelly E. Seaton

    (Human Vaccine Institute, Duke University)

  • Brandy M. Ward

    (Duke University)

  • Robert T. Bailer

    (Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA)

  • Raphael Gottardo

    (Fred Hutchison Cancer Research Center)

  • Wenjuan Gu

    (Biostatistics Research Branch, NIAID, NIH, Bethesda, Maryland 20892, USA)

  • Guido Ferrari

    (Duke University)

  • S. Munir Alam

    (Human Vaccine Institute, Duke University)

  • Thomas N. Denny

    (Human Vaccine Institute, Duke University)

  • David C. Montefiori

    (Duke University)

  • Georgia D. Tomaras

    (Human Vaccine Institute, Duke University)

  • Bette T. Korber

    (Los Alamos National Laboratories)

  • Martha C. Nason

    (Biostatistics Research Branch, NIAID, NIH, Bethesda, Maryland 20892, USA)

  • Robert A. Seder

    (Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA)

  • Richard A. Koup

    (Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA)

  • Norman L. Letvin

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center)

  • Srinivas S. Rao

    (Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA)

  • Gary J. Nabel

    (Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA
    Present address: Sanofi-Pasteur, Cambridge, Massachusetts 02139, USA.)

  • John R. Mascola

    (Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA)

Abstract

A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that antibodies to the SIV envelope are necessary and sufficient to prevent infection. Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two-amino-acid signature that alters antigenicity and confers neutralization resistance. A similar signature confers resistance of human immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine-elicited or naturally elicited antibodies. These analyses provide insight into the limited efficacy seen in HIV vaccine trials.

Suggested Citation

  • Mario Roederer & Brandon F. Keele & Stephen D. Schmidt & Rosemarie D. Mason & Hugh C. Welles & Will Fischer & Celia Labranche & Kathryn E. Foulds & Mark K. Louder & Zhi-Yong Yang & John-Paul M. Todd &, 2014. "Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV," Nature, Nature, vol. 505(7484), pages 502-508, January.
    • Handle: RePEc:nat:nature:v:505:y:2014:i:7484:d:10.1038_nature12893
    DOI: 10.1038/nature12893
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    Cited by:

    1. Fangzhu Zhao & Zachary T. Berndsen & Nuria Pedreño-Lopez & Alison Burns & Joel D. Allen & Shawn Barman & Wen-Hsin Lee & Srirupa Chakraborty & Sandrasegaram Gnanakaran & Leigh M. Sewall & Gabriel Ozoro, 2022. "Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Svenja Weiss & Vincenza Itri & Ruimin Pan & Xunqing Jiang & Christina C. Luo & Lynn Morris & Delphine C. Malherbe & Philip Barnette & Jeff Alexander & Xiang-Peng Kong & Nancy L. Haigwood & Ann J. Hess, 2022. "Differential V2-directed antibody responses in non-human primates infected with SHIVs or immunized with diverse HIV vaccines," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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