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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
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.

0969-2126
1-13
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.
09e75998-09b0-465f-a059-c89b07f3b2c3
Cottrell, Christopher A.
942bfa7b-c09e-459d-a6c2-0d64d55fa230
van Gils, Marit J.
f2e1e7f1-36a1-4270-8509-d17a10ddb9a6
D'addabbo, Alessio
ae2358c9-d733-4c7f-aaf3-b8b52b7cb810
Harvey, David J.
8bb24417-3852-4b1f-827b-0d5d2c176744
Behrens, Anna-Janina
ed584c40-79cb-4de9-bb9c-bd68c71d6a68
Allen, Joel D.
c873d886-2a66-475b-ae04-57a10b37e716
Watanabe, Yasunori
8c0ee4af-a293-4de5-9036-3ce2051b380c
Scaringi, Nicole
e7fa8e37-da05-420d-90ef-c8c85909de4d
Polveroni, Thomas M.
e04f1f4d-92d7-476d-9eb0-4cb219fa70d8
Maker, Allison
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Vasiljevic, Snezana
17e075b4-520d-4b9b-a4a7-08ac394ae5e1
de Val, Natalia
17ca4fc8-dfab-41dc-aa68-26de0e9a265c
Sanders, Rogier W.
d3b67c2c-c725-42e7-b972-50b30be67c74
Ward, Andrew B.
78ce5b6a-b852-4ee4-a950-f7ff7b183d83
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9

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, 1-13. (doi:10.1016/j.str.2020.04.022).

Record type: Article

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.

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Accepted/In Press date: 28 April 2020
e-pub ahead of print date: 19 May 2020

Identifiers

Local EPrints ID: 441327
URI: http://eprints.soton.ac.uk/id/eprint/441327
ISSN: 0969-2126
PURE UUID: 7b7b1885-e700-4581-81d4-b8f448ae448d
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

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Date deposited: 09 Jun 2020 16:31
Last modified: 07 Oct 2020 02:15

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Contributors

Author: Gemma E. Seabright
Author: Christopher A. Cottrell
Author: Marit J. van Gils
Author: Alessio D'addabbo
Author: David J. Harvey
Author: Anna-Janina Behrens
Author: Joel D. Allen
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
Author: Max Crispin ORCID iD

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