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:10.1016/j.str.2020.04.022

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

Structure. 2020 Aug 4;28(8):897-909.e6. doi: 10.1016/j.str.2020.04.022. Epub 2020 May 19.

Authors

Gemma E Seabright¹, Christopher A Cottrell², Marit J van Gils³, Alessio D'addabbo⁴, David J Harvey⁵, Anna-Janina Behrens⁶, Joel D Allen⁴, Yasunori Watanabe¹, Nicole Scaringi², Thomas M Polveroni², Allison Maker⁶, Snezana Vasiljevic⁶, Natalia de Val⁷, Rogier W Sanders⁸, Andrew B Ward², Max Crispin⁹

Affiliations

¹ School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
² Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA 92037, USA.
³ Department of Medical Microbiology, Amsterdam UMC, AMC, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands.
⁴ School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
⁵ School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7FZ, UK.
⁶ Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
⁷ Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD 21701, USA; Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁸ Department of Medical Microbiology, Amsterdam UMC, AMC, University of Amsterdam, Amsterdam 1105 AZ, The Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
⁹ School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. Electronic address: [email protected].

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal / chemistry
Antibodies, Monoclonal / immunology
Antigen-Antibody Complex / chemistry
Broadly Neutralizing Antibodies / chemistry
Broadly Neutralizing Antibodies / immunology
Epitopes / chemistry*
Epitopes / genetics
Epitopes / immunology
HEK293 Cells
HIV Antibodies / chemistry
HIV Antibodies / immunology
HIV-1 / immunology*
Humans
Molecular Docking Simulation
Mutation
Polysaccharides / chemistry*
Polysaccharides / immunology
env Gene Products, Human Immunodeficiency Virus / chemistry*
env Gene Products, Human Immunodeficiency Virus / genetics
env Gene Products, Human Immunodeficiency Virus / immunology

Substances

2G12 monoclonal antibody
Antibodies, Monoclonal
Antigen-Antibody Complex
Broadly Neutralizing Antibodies
Epitopes
HIV Antibodies
Polysaccharides
env Gene Products, Human Immunodeficiency Virus

Abstract

Publication types

MeSH terms

Substances

Grants and funding