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Natural variation in Fc glycosylation of HIV-specific antibodies impacts antiviral activity

Natural variation in Fc glycosylation of HIV-specific antibodies impacts antiviral activity
Natural variation in Fc glycosylation of HIV-specific antibodies impacts antiviral activity

While the induction of a neutralizing antibody response against HIV remains a daunting goal, data from both natural infection and vaccine-induced immune responses suggest that it may be possible to induce antibodies with enhanced Fc effector activity and improved antiviral control via vaccination. However, the specific features of naturally induced HIV-specific antibodies that allow for the potent recruitment of antiviral activity and the means by which these functions are regulated are poorly defined. Because antibody effector functions are critically dependent on antibody Fc domain glycosylation, we aimed to define the natural glycoforms associated with robust Fc-mediated antiviral activity. We demonstrate that spontaneous control of HIV and improved antiviral activity are associated with a dramatic shift in the global antibody-glycosylation profile toward agalac-tosylated glycoforms. HIV-specific antibodies exhibited an even greater frequency of agalactosylated, afucosylated, and asialylated glycans. These glycoforms were associated with enhanced Fc-mediated reduction of viral replication and enhanced Fc receptor binding and were consistent with transcriptional profiling of glycosyl-transferases in peripheral B cells. These data suggest that B cell programs tune antibody glycosylation actively in an antigen-specific manner, potentially contributing to antiviral control during HIV infection.

0021-9738
2183-2192
Ackerman, Margaret E.
b4a13358-a1ad-4b11-867b-e3102c2c9961
Crispin, Matthew
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Yu, Xiaojie
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Baruah, Kavitha
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Boesch, Austin W.
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Harvey, David J.
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Dugast, Anne Sophie
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Heizen, Erin L.
37b8489a-24dd-44a0-b973-d939682ae401
Ercan, Altan
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Choi, Ickwon
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Streeck, Hendrik
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Nigrovic, Peter A.
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Bailey-Kellogg, Chris
b41c743e-a877-4e73-a59f-0de25ef9b31c
Scanlan, Chris
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Alter, Galit
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Ackerman, Margaret E.
b4a13358-a1ad-4b11-867b-e3102c2c9961
Crispin, Matthew
cd980957-0943-4b89-b2b2-710f01f33bc9
Yu, Xiaojie
44d52374-eacc-4e23-b7da-c881e6d3a5dd
Baruah, Kavitha
a02f59f3-5e0f-4735-9fdd-639bdbb8f563
Boesch, Austin W.
1a113318-e5e3-47da-9a2c-db9a6e3230a0
Harvey, David J.
8bb24417-3852-4b1f-827b-0d5d2c176744
Dugast, Anne Sophie
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Heizen, Erin L.
37b8489a-24dd-44a0-b973-d939682ae401
Ercan, Altan
44f9f425-ad93-48f1-866f-f1c3f39586bf
Choi, Ickwon
8de2014f-0b6f-4f06-9340-90e22100cf75
Streeck, Hendrik
1eabd300-75d3-4017-a2dc-f50c526f4446
Nigrovic, Peter A.
4ef2dfde-f17b-4fc2-aea7-61022336d32d
Bailey-Kellogg, Chris
b41c743e-a877-4e73-a59f-0de25ef9b31c
Scanlan, Chris
d703ed2d-5d1d-471e-9fb2-09f59a70861a
Alter, Galit
2742863e-d5cf-4419-b922-9679afa2bc4b

Ackerman, Margaret E., Crispin, Matthew, Yu, Xiaojie, Baruah, Kavitha, Boesch, Austin W., Harvey, David J., Dugast, Anne Sophie, Heizen, Erin L., Ercan, Altan, Choi, Ickwon, Streeck, Hendrik, Nigrovic, Peter A., Bailey-Kellogg, Chris, Scanlan, Chris and Alter, Galit (2013) Natural variation in Fc glycosylation of HIV-specific antibodies impacts antiviral activity. Journal of Clinical Investigation, 123 (5), 2183-2192. (doi:10.1172/JCI65708).

Record type: Article

Abstract

While the induction of a neutralizing antibody response against HIV remains a daunting goal, data from both natural infection and vaccine-induced immune responses suggest that it may be possible to induce antibodies with enhanced Fc effector activity and improved antiviral control via vaccination. However, the specific features of naturally induced HIV-specific antibodies that allow for the potent recruitment of antiviral activity and the means by which these functions are regulated are poorly defined. Because antibody effector functions are critically dependent on antibody Fc domain glycosylation, we aimed to define the natural glycoforms associated with robust Fc-mediated antiviral activity. We demonstrate that spontaneous control of HIV and improved antiviral activity are associated with a dramatic shift in the global antibody-glycosylation profile toward agalac-tosylated glycoforms. HIV-specific antibodies exhibited an even greater frequency of agalactosylated, afucosylated, and asialylated glycans. These glycoforms were associated with enhanced Fc-mediated reduction of viral replication and enhanced Fc receptor binding and were consistent with transcriptional profiling of glycosyl-transferases in peripheral B cells. These data suggest that B cell programs tune antibody glycosylation actively in an antigen-specific manner, potentially contributing to antiviral control during HIV infection.

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More information

Published date: 1 May 2013

Identifiers

Local EPrints ID: 414598
URI: https://eprints.soton.ac.uk/id/eprint/414598
ISSN: 0021-9738
PURE UUID: e2f3fc89-fc33-49fa-a5bc-a05929434cbe
ORCID for Matthew Crispin: ORCID iD orcid.org/0000-0002-1072-2694

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Date deposited: 04 Oct 2017 16:30
Last modified: 14 Mar 2019 01:25

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Contributors

Author: Margaret E. Ackerman
Author: Matthew Crispin ORCID iD
Author: Xiaojie Yu
Author: Kavitha Baruah
Author: Austin W. Boesch
Author: David J. Harvey
Author: Anne Sophie Dugast
Author: Erin L. Heizen
Author: Altan Ercan
Author: Ickwon Choi
Author: Hendrik Streeck
Author: Peter A. Nigrovic
Author: Chris Bailey-Kellogg
Author: Chris Scanlan
Author: Galit Alter

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