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

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 J. Crispin, Thomas A. Bowden, Christopher N. Scanlan, Andrew B. Ward, William R. Schief, Katie J. Doores () and Max Crispin ()
Additional contact information
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
Sergey Menis: 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
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

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8479

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