Networks of HIV-1 envelope glycans maintain antibody epitopes in the face of glycan additions and deletions
Networks of HIV-1 envelope glycans maintain antibody epitopes in the face of glycan additions and deletions
Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike. Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans. Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets. Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network. In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans. Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.
broadly neutralizing antibodies, cryo-electron microscopy, glycans, glycosylation, human immunodeficiency virus, mass spectrometry, structure, vaccines
897-909.e6
Seabright, Gemma E.
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Cottrell, Christopher A.
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van Gils, Marit J.
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D'addabbo, Alessio
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Harvey, David J.
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Behrens, Anna-Janina
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Allen, Joel D.
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Watanabe, Yasunori
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Scaringi, Nicole
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Polveroni, Thomas M.
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Maker, Allison
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Vasiljevic, Snezana
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de Val, Natalia
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Sanders, Rogier W.
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Ward, Andrew B.
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Crispin, Max
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4 August 2020
Seabright, Gemma E.
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Cottrell, Christopher A.
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van Gils, Marit J.
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D'addabbo, Alessio
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Harvey, David J.
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Behrens, Anna-Janina
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Allen, Joel D.
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Watanabe, Yasunori
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Scaringi, Nicole
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Polveroni, Thomas M.
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Maker, Allison
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Vasiljevic, Snezana
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de Val, Natalia
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Sanders, Rogier W.
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Ward, Andrew B.
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Crispin, Max
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Seabright, Gemma E., Cottrell, Christopher A., van Gils, Marit J., D'addabbo, Alessio, Harvey, David J., Behrens, Anna-Janina, Allen, Joel D., Watanabe, Yasunori, Scaringi, Nicole, Polveroni, Thomas M., Maker, Allison, Vasiljevic, Snezana, de Val, Natalia, Sanders, Rogier W., Ward, Andrew B. and Crispin, Max
(2020)
Networks of HIV-1 envelope glycans maintain antibody epitopes in the face of glycan additions and deletions.
Structure, 28 (8), .
(doi:10.1016/j.str.2020.04.022).
Abstract
Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike. Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans. Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets. Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network. In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans. Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.
Text
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More information
Accepted/In Press date: 28 April 2020
e-pub ahead of print date: 19 May 2020
Published date: 4 August 2020
Keywords:
broadly neutralizing antibodies, cryo-electron microscopy, glycans, glycosylation, human immunodeficiency virus, mass spectrometry, structure, vaccines
Identifiers
Local EPrints ID: 441327
URI: http://eprints.soton.ac.uk/id/eprint/441327
ISSN: 0969-2126
PURE UUID: 7b7b1885-e700-4581-81d4-b8f448ae448d
Catalogue record
Date deposited: 09 Jun 2020 16:31
Last modified: 02 May 2024 02:00
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Contributors
Author:
Gemma E. Seabright
Author:
Christopher A. Cottrell
Author:
Marit J. van Gils
Author:
David J. Harvey
Author:
Anna-Janina Behrens
Author:
Yasunori Watanabe
Author:
Nicole Scaringi
Author:
Thomas M. Polveroni
Author:
Allison Maker
Author:
Snezana Vasiljevic
Author:
Natalia de Val
Author:
Rogier W. Sanders
Author:
Andrew B. Ward
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