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Antibody neutralization and escape by HIV-1

Author

Listed:
  • Xiping Wei

    (University of Alabama at Birmingham)

  • Julie M. Decker

    (University of Alabama at Birmingham)

  • Shuyi Wang

    (University of Alabama at Birmingham)

  • Huxiong Hui

    (University of Alabama at Birmingham)

  • John C. Kappes

    (University of Alabama at Birmingham
    University of Alabama at Birmingham)

  • Xiaoyun Wu

    (University of Alabama at Birmingham)

  • Jesus F. Salazar-Gonzalez

    (University of Alabama at Birmingham)

  • Maria G. Salazar

    (University of Alabama at Birmingham)

  • J. Michael Kilby

    (University of Alabama at Birmingham)

  • Michael S. Saag

    (University of Alabama at Birmingham)

  • Natalia L. Komarova

    (Institute for Advanced Study)

  • Martin A. Nowak

    (Institute for Advanced Study)

  • Beatrice H. Hahn

    (University of Alabama at Birmingham
    University of Alabama at Birmingham)

  • Peter D. Kwong

    (Vaccine Research Center, National Institutes of Health)

  • George M. Shaw

    (University of Alabama at Birmingham
    University of Alabama at Birmingham
    University of Alabama at Birmingham)

Abstract

Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens, yet their role in HIV-1 infection is unclear1,2,3,4,5,6. To gain a better understanding of this role, we examined plasma from patients with acute HIV infection. Here we report the detection of autologous Nab as early as 52 days after detection of HIV-specific antibodies. The viral inhibitory activity of Nab resulted in complete replacement of neutralization-sensitive virus by successive populations of resistant virus. Escape virus contained mutations in the env gene that were unexpectedly sparse, did not map generally to known neutralization epitopes, and involved primarily changes in N-linked glycosylation. This pattern of escape, and the exceptional density of HIV-1 envelope glycosylation generally7,8, led us to postulate an evolving ‘glycan shield’ mechanism of neutralization escape whereby selected changes in glycan packing prevent Nab binding but not receptor binding. Direct support for this model was obtained by mutational substitution showing that Nab-selected alterations in glycosylation conferred escape from both autologous antibody and epitope-specific monoclonal antibodies. The evolving glycan shield thus represents a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire.

Suggested Citation

  • Xiping Wei & Julie M. Decker & Shuyi Wang & Huxiong Hui & John C. Kappes & Xiaoyun Wu & Jesus F. Salazar-Gonzalez & Maria G. Salazar & J. Michael Kilby & Michael S. Saag & Natalia L. Komarova & Martin, 2003. "Antibody neutralization and escape by HIV-1," Nature, Nature, vol. 422(6929), pages 307-312, March.
  • Handle: RePEc:nat:nature:v:422:y:2003:i:6929:d:10.1038_nature01470
    DOI: 10.1038/nature01470
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    Citations

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    Cited by:

    1. Jeffrey E. Harris, 2021. "The Repeated Setbacks of HIV Vaccine Development Laid the Groundwork for SARS-CoV-2 Vaccines," NBER Working Papers 28587, National Bureau of Economic Research, Inc.
    2. Yi-Nan Zhang & Jennifer Paynter & Aleksandar Antanasijevic & Joel D. Allen & Mor Eldad & Yi-Zong Lee & Jeffrey Copps & Maddy L. Newby & Linling He & Deborah Chavez & Pat Frost & Anna Goodroe & John Du, 2023. "Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimers as HIV-1 vaccine candidates," Nature Communications, Nature, vol. 14(1), pages 1-29, December.
    3. Wayne Delport & Konrad Scheffler & Cathal Seoighe, 2008. "Frequent Toggling between Alternative Amino Acids Is Driven by Selection in HIV-1," PLOS Pathogens, Public Library of Science, vol. 4(12), pages 1-13, December.
    4. Kun-Wei Chan & Christina C. Luo & Hong Lu & Xueling Wu & Xiang-Peng Kong, 2021. "A site of vulnerability at V3 crown defined by HIV-1 bNAb M4008_N1," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    5. Shixia Wang & Kun-Wei Chan & Danlan Wei & Xiuwen Ma & Shuying Liu & Guangnan Hu & Saeyoung Park & Ruimin Pan & Ying Gu & Alexandra F. Nazzari & Adam S. Olia & Kai Xu & Bob C. Lin & Mark K. Louder & Kr, 2024. "Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    6. David A. Spencer & Benjamin S. Goldberg & Shilpi Pandey & Tracy Ordonez & Jérémy Dufloo & Philip Barnette & William F. Sutton & Heidi Henderson & Rebecca Agnor & Lina Gao & Timothée Bruel & Olivier Sc, 2022. "Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. Shuang Yang & Giorgos Hiotis & Yi Wang & Junjian Chen & Jia-huai Wang & Mikyung Kim & Ellis L. Reinherz & Thomas Walz, 2022. "Dynamic HIV-1 spike motion creates vulnerability for its membrane-bound tripod to antibody attack," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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