Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions

Gemma E. Seabright; Christopher A. Cottrell; Marit J. van Gils; Alessio D'addabbo; David J. Harvey; Anna-Janina Behrens; Joel D. Allen; Yasunori Watanabe; Nicole Scaringi; Thomas M. Polveroni; Allison Maker; Snezana Vasiljevic; Natalia de Val; Rogier W. Sanders; Andrew B. Ward; Max Crispin

doi:https://doi.org/10.1016/j.str.2020.04.022

Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions

Gemma E. Seabright, Christopher A. Cottrell, Marit J. van Gils, Alessio D'addabbo, David J. Harvey, Anna-Janina Behrens, Joel D. Allen, Yasunori Watanabe, Nicole Scaringi, Thomas M. Polveroni, Allison Maker, Snezana Vasiljevic, Natalia de Val, Rogier W. Sanders, Andrew B. Ward, Max Crispin

Research output: Contribution to journal › Article › Academic › peer-review

37 Citations (Scopus)

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.

Original language	English
Pages (from-to)	897-909.e6
Journal	Structure (London, England
Volume	28
Issue number	8
Early online date	2020
DOIs	https://doi.org/10.1016/j.str.2020.04.022
Publication status	Published - 4 Aug 2020

Keywords

broadly neutralizing antibodies
cryo-electron microscopy
glycans
glycosylation
human immunodeficiency virus
mass spectrometry
structure
vaccines

Access to Document

https://doi.org/10.1016/j.str.2020.04.022

Cite this

Seabright, G. E., Cottrell, C. A., van Gils, M. J., D'addabbo, A., Harvey, D. J., Behrens, A.-J., Allen, J. D., Watanabe, Y., Scaringi, N., Polveroni, T. M., Maker, A., Vasiljevic, S., de Val, N., Sanders, R. W., Ward, A. B., & Crispin, M. (2020). Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions. Structure (London, England, 28(8), 897-909.e6. https://doi.org/10.1016/j.str.2020.04.022

@article{f5d655130ba046b8aabc8227c9b5c464,

title = "Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions",

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.",

keywords = "broadly neutralizing antibodies, cryo-electron microscopy, glycans, glycosylation, human immunodeficiency virus, mass spectrometry, structure, vaccines",

author = "Seabright, {Gemma E.} and Cottrell, {Christopher A.} and {van Gils}, {Marit J.} and Alessio D'addabbo and Harvey, {David J.} and Anna-Janina Behrens and Allen, {Joel D.} and Yasunori Watanabe and Nicole Scaringi and Polveroni, {Thomas M.} and Allison Maker and Snezana Vasiljevic and {de Val}, Natalia and Sanders, {Rogier W.} and Ward, {Andrew B.} and Max Crispin",

year = "2020",

month = aug,

day = "4",

doi = "https://doi.org/10.1016/j.str.2020.04.022",

language = "English",

volume = "28",

pages = "897--909.e6",

journal = "Structure (London, England",

issn = "0969-2126",

publisher = "Cell Press",

number = "8",

}

Seabright, GE, Cottrell, CA, van Gils, MJ, D'addabbo, A, Harvey, DJ, Behrens, A-J, Allen, JD, Watanabe, Y, Scaringi, N, Polveroni, TM, Maker, A, Vasiljevic, S, de Val, N, Sanders, RW, Ward, AB & Crispin, M 2020, 'Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions', Structure (London, England, vol. 28, no. 8, pp. 897-909.e6. https://doi.org/10.1016/j.str.2020.04.022

TY - JOUR

T1 - Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions

AU - Seabright, Gemma E.

AU - Cottrell, Christopher A.

AU - van Gils, Marit J.

AU - D'addabbo, Alessio

AU - Harvey, David J.

AU - Behrens, Anna-Janina

AU - Allen, Joel D.

AU - Watanabe, Yasunori

AU - Scaringi, Nicole

AU - Polveroni, Thomas M.

AU - Maker, Allison

AU - Vasiljevic, Snezana

AU - de Val, Natalia

AU - Sanders, Rogier W.

AU - Ward, Andrew B.

AU - Crispin, Max

PY - 2020/8/4

Y1 - 2020/8/4

N2 - 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.

AB - 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.

KW - broadly neutralizing antibodies

KW - cryo-electron microscopy

KW - glycans

KW - glycosylation

KW - human immunodeficiency virus

KW - mass spectrometry

KW - structure

KW - vaccines

UR - http://www.scopus.com/inward/record.url?scp=85085753454&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.str.2020.04.022

DO - https://doi.org/10.1016/j.str.2020.04.022

M3 - Article

C2 - 32433992

SN - 0969-2126

VL - 28

SP - 897-909.e6

JO - Structure (London, England

JF - Structure (London, England

IS - 8

ER -

Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions

Abstract

Keywords

Access to Document

Other files and links

Cite this