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Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies

Author

Listed:
  • Laura K. Pritchard

    (Oxford Glycobiology Institute, University of Oxford)

  • Daniel I.R. Spencer

    (Ludger Ltd., Culham Science Centre)

  • Louise Royle

    (Ludger Ltd., Culham Science Centre)

  • Camille Bonomelli

    (Oxford Glycobiology Institute, University of Oxford)

  • Gemma E. Seabright

    (Oxford Glycobiology Institute, University of Oxford)

  • Anna-Janina Behrens

    (Oxford Glycobiology Institute, University of Oxford)

  • Daniel W. Kulp

    (The Scripps Research Institute
    Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute)

  • Sergey Menis

    (The Scripps Research Institute
    Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute)

  • Stefanie A. Krumm

    (King’s College London School of Medicine at Guy’s, King’s and St Thomas’ Hospitals, Guy’s Hospital, Great Maze Pond)

  • D. Cameron Dunlop

    (Oxford Glycobiology Institute, University of Oxford)

  • Daniel J. Crispin

    (Oxford Glycobiology Institute, University of Oxford)

  • Thomas A. Bowden

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Christopher N. Scanlan

    (Oxford Glycobiology Institute, University of Oxford)

  • Andrew B. Ward

    (IAVI Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Skaggs Institute for Chemical Biology, The Scripps Research Institute)

  • William R. Schief

    (The Scripps Research Institute
    Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute
    Ragon Institute of MGH, MIT and Harvard)

  • Katie J. Doores

    (King’s College London School of Medicine at Guy’s, King’s and St Thomas’ Hospitals, Guy’s Hospital, Great Maze Pond)

  • Max Crispin

    (Oxford Glycobiology Institute, University of Oxford)

Abstract

The envelope spike of HIV-1 employs a ‘glycan shield’ to protect itself from antibody-mediated neutralization. Paradoxically, however, potent broadly neutralizing antibodies (bnAbs) that target this shield have been isolated. The unusually high glycan density on the gp120 subunit limits processing during biosynthesis, leaving a region of under-processed oligomannose-type structures, which is a primary target of these bnAbs. Here we investigate the contribution of individual glycosylation sites in the formation of this so-called intrinsic mannose patch. Deletion of individual sites has a limited effect on the overall size of the intrinsic mannose patch but leads to changes in the processing of neighbouring glycans. These structural changes are largely tolerated by a panel of glycan-dependent bnAbs targeting these regions, indicating a degree of plasticity in their recognition. These results support the intrinsic mannose patch as a stable target for vaccine design.

Suggested Citation

  • Laura K. Pritchard & Daniel I.R. Spencer & Louise Royle & Camille Bonomelli & Gemma E. Seabright & Anna-Janina Behrens & Daniel W. Kulp & Sergey Menis & Stefanie A. Krumm & D. Cameron Dunlop & Daniel , 2015. "Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8479
    DOI: 10.1038/ncomms8479
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    Cited by:

    1. Wen-Han Yu & Peng Zhao & Monia Draghi & Claudia Arevalo & Christina B Karsten & Todd J Suscovich & Bronwyn Gunn & Hendrik Streeck & Abraham L Brass & Michael Tiemeyer & Michael Seaman & John R Mascola, 2018. "Exploiting glycan topography for computational design of Env glycoprotein antigenicity," PLOS Computational Biology, Public Library of Science, vol. 14(4), pages 1-28, April.
    2. Kwinten Sliepen & Laura Radić & Joan Capella-Pujol & Yasunori Watanabe & Ian Zon & Ana Chumbe & Wen-Hsin Lee & Marlon Gast & Jelle Koopsen & Sylvie Koekkoek & Iván Moral-Sánchez & Philip J. M. Brouwer, 2022. "Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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