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Integrity of glycosylation processing of a glycan-depleted trimeric HIV-1 immunogen targeting key B-cell lineages

Integrity of glycosylation processing of a glycan-depleted trimeric HIV-1 immunogen targeting key B-cell lineages
Integrity of glycosylation processing of a glycan-depleted trimeric HIV-1 immunogen targeting key B-cell lineages

Broadly neutralizing antibodies (bNAbs) that target the trimeric HIV-1 envelope glycoprotein spike (Env) are tools that can guide the design of recombinant Env proteins intended to engage the predicted human germline precursors of bNAbs (gl-bNAbs). The protein components of gl-bNAb epitopes are often masked by glycans, while mature bNAbs can evolve to accommodate or bypass these shielding glycans. The design of germline-targeting Env immunogens therefore includes the targeted deletion of specific glycan sites. However, the processing of glycans on Env trimers can be influenced by the density with which they are packed together, a highly relevant point given the essential contributions under-processed glycans make to multiple bNAb epitopes. We sought to determine the impact of the removal of 15 potential N-glycan sites (5 per protomer) from the germline-targeting soluble trimer, BG505 SOSIP.v4.1-GT1, using quantitative, site-specific N-glycan mass spectrometry analysis. We find that, compared with SOSIP.664, there was little overall change in the glycan profile but only subtle increases in the extent of processing at sites immediately adjacent to where glycans had been deleted. We conclude that multiple glycans can be deleted from BG505 SOSIP trimers without perturbing the overall integrity of the glycan shield.

Journal Article
1535-3893
987-999
Behrens, Anna-Janina
ed584c40-79cb-4de9-bb9c-bd68c71d6a68
Kumar, Abhinav
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Medina-Ramirez, Max
bd603493-0191-4117-b9d3-3e991b406ec8
Cupo, Albert
aa9f476e-3296-4118-9231-0edc774b8335
Marshall, Kevin
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Cruz Portillo, Victor M
9e75922a-3b79-4f9a-8711-a49bcc051ec8
Harvey, David J.
261201b9-2ec2-4f49-bd32-eadac805da98
Ozorowski, Gabriel
9d448a80-7310-4b30-ba44-ee8b18222a02
Zitzmann, Nicole
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Wilson, Ian A.
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Ward, Andrew B.
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Struwe, Weston B.
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Moore, John P.
3c26226c-c036-48db-bbd1-828a86b29697
Sanders, Rogier W.
d3b67c2c-c725-42e7-b972-50b30be67c74
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Behrens, Anna-Janina
ed584c40-79cb-4de9-bb9c-bd68c71d6a68
Kumar, Abhinav
22f8d17d-11d5-4c38-8b5c-ea479bd60bad
Medina-Ramirez, Max
bd603493-0191-4117-b9d3-3e991b406ec8
Cupo, Albert
aa9f476e-3296-4118-9231-0edc774b8335
Marshall, Kevin
54d79b92-b709-438e-96e5-ce33a64e7a8e
Cruz Portillo, Victor M
9e75922a-3b79-4f9a-8711-a49bcc051ec8
Harvey, David J.
261201b9-2ec2-4f49-bd32-eadac805da98
Ozorowski, Gabriel
9d448a80-7310-4b30-ba44-ee8b18222a02
Zitzmann, Nicole
f20f9920-574a-4aac-a86f-1625dd60125c
Wilson, Ian A.
7865d500-d638-4a67-ad6d-fefad0ae83bb
Ward, Andrew B.
78ce5b6a-b852-4ee4-a950-f7ff7b183d83
Struwe, Weston B.
16a348b1-3921-4a2d-b5fb-d341fccea65f
Moore, John P.
3c26226c-c036-48db-bbd1-828a86b29697
Sanders, Rogier W.
d3b67c2c-c725-42e7-b972-50b30be67c74
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9

Behrens, Anna-Janina, Kumar, Abhinav, Medina-Ramirez, Max, Cupo, Albert, Marshall, Kevin, Cruz Portillo, Victor M, Harvey, David J., Ozorowski, Gabriel, Zitzmann, Nicole, Wilson, Ian A., Ward, Andrew B., Struwe, Weston B., Moore, John P., Sanders, Rogier W. and Crispin, Max (2018) Integrity of glycosylation processing of a glycan-depleted trimeric HIV-1 immunogen targeting key B-cell lineages. Journal of Proteome Research, 17 (3), 987-999. (doi:10.1021/acs.jproteome.7b00639).

Record type: Article

Abstract

Broadly neutralizing antibodies (bNAbs) that target the trimeric HIV-1 envelope glycoprotein spike (Env) are tools that can guide the design of recombinant Env proteins intended to engage the predicted human germline precursors of bNAbs (gl-bNAbs). The protein components of gl-bNAb epitopes are often masked by glycans, while mature bNAbs can evolve to accommodate or bypass these shielding glycans. The design of germline-targeting Env immunogens therefore includes the targeted deletion of specific glycan sites. However, the processing of glycans on Env trimers can be influenced by the density with which they are packed together, a highly relevant point given the essential contributions under-processed glycans make to multiple bNAb epitopes. We sought to determine the impact of the removal of 15 potential N-glycan sites (5 per protomer) from the germline-targeting soluble trimer, BG505 SOSIP.v4.1-GT1, using quantitative, site-specific N-glycan mass spectrometry analysis. We find that, compared with SOSIP.664, there was little overall change in the glycan profile but only subtle increases in the extent of processing at sites immediately adjacent to where glycans had been deleted. We conclude that multiple glycans can be deleted from BG505 SOSIP trimers without perturbing the overall integrity of the glycan shield.

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Behrens_JProt_2018_NIHMS946942_new - Accepted Manuscript
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Accepted/In Press date: 6 February 2018
e-pub ahead of print date: 8 February 2018
Published date: 2018
Keywords: Journal Article

Identifiers

Local EPrints ID: 418537
URI: https://eprints.soton.ac.uk/id/eprint/418537
ISSN: 1535-3893
PURE UUID: 419ae1ef-de2d-4649-8968-27a717a668b0
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

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Date deposited: 09 Mar 2018 17:31
Last modified: 14 Mar 2019 05:15

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Contributors

Author: Anna-Janina Behrens
Author: Abhinav Kumar
Author: Max Medina-Ramirez
Author: Albert Cupo
Author: Kevin Marshall
Author: Victor M Cruz Portillo
Author: David J. Harvey
Author: Gabriel Ozorowski
Author: Nicole Zitzmann
Author: Ian A. Wilson
Author: Andrew B. Ward
Author: Weston B. Struwe
Author: John P. Moore
Author: Rogier W. Sanders
Author: Max Crispin ORCID iD

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