HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound

Rasmus Offersen; Wen Han Yu; Eileen P. Scully; Boris Julg; Zelda Euler; Saheli Sadanand; Dario Garcia-Dominguez; Lu Zheng; Thomas A. Rasmussen; Madeleine F. Jennewein; Caitlyn Linde; Jessica Sassic; Giuseppe Lofano; Selena Vigano; Kathryn E. Stephenson; Stephanie Fischinger; Todd J. Suscovich; Mathias Lichterfeld; Douglas Lauffenburger; Erik S. Rosenberg; Todd Allen; Marcus Altfeld; Richelle C. Charles; Lars Østergaard; Martin Tolstrup; Dan H. Barouch; Ole S. Søgaard; Galit Alter

doi:10.1016/j.celrep.2020.108502

HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound

Rasmus Offersen, Wen Han Yu, Eileen P. Scully, Boris Julg, Zelda Euler, Saheli Sadanand, Dario Garcia-Dominguez, Lu Zheng, Thomas A. Rasmussen, Madeleine F. Jennewein, Caitlyn Linde, Jessica Sassic, Giuseppe Lofano, Selena Vigano, Kathryn E. Stephenson, Stephanie Fischinger, Todd J. Suscovich, Mathias Lichterfeld, Douglas Lauffenburger, Erik S. RosenbergTodd Allen, Marcus Altfeld, Richelle C. Charles, Lars Østergaard, Martin Tolstrup, Dan H. Barouch, Ole S. Søgaard, Galit Alter

School of Medicine

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

1 Scopus citations

Abstract

Changes in antibody glycosylation are linked to inflammation across several diseases. Alterations in bulk antibody galactosylation can predict rheumatic flares, act as a sensor for immune activation, predict gastric cancer relapse, track with biological age, shift with vaccination, change with HIV reservoir size on therapy, and decrease in HIV and HCV infections. However, whether changes in antibody Fc biology also track with reservoir rebound time remains unclear. The identification of a biomarker that could forecast viral rebound time could significantly accelerate the downselection and iterative improvement of promising HIV viral eradication strategies. Using a comprehensive antibody Fc-profiling approach, the level of HIV-specific antibody Fc N-galactosylation is significantly associated with time to rebound after treatment discontinuation across three independent cohorts. Thus virus-specific antibody glycosylation may represent a promising, simply measured marker to track reservoir reactivation.

Original language	English (US)
Article number	108502
Journal	Cell Reports
Volume	33
Issue number	11
DOIs	https://doi.org/10.1016/j.celrep.2020.108502
State	Published - Dec 15 2020

Keywords

B cells
Fc-receptors
HIV
HIV remission
HIV reservoir
antibodies
biomarkers
cure
glycosylation
viral host response

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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Offersen, R., Yu, W. H., Scully, E. P., Julg, B., Euler, Z., Sadanand, S., Garcia-Dominguez, D., Zheng, L., Rasmussen, T. A., Jennewein, M. F., Linde, C., Sassic, J., Lofano, G., Vigano, S., Stephenson, K. E., Fischinger, S., Suscovich, T. J., Lichterfeld, M., Lauffenburger, D., ... Alter, G. (2020). HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound. Cell Reports, 33(11), Article 108502. https://doi.org/10.1016/j.celrep.2020.108502

Offersen, R, Yu, WH, Scully, EP, Julg, B, Euler, Z, Sadanand, S, Garcia-Dominguez, D, Zheng, L, Rasmussen, TA, Jennewein, MF, Linde, C, Sassic, J, Lofano, G, Vigano, S, Stephenson, KE, Fischinger, S, Suscovich, TJ, Lichterfeld, M, Lauffenburger, D, Rosenberg, ES, Allen, T, Altfeld, M, Charles, RC, Østergaard, L, Tolstrup, M, Barouch, DH, Søgaard, OS & Alter, G 2020, 'HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound', Cell Reports, vol. 33, no. 11, 108502. https://doi.org/10.1016/j.celrep.2020.108502

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title = "HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound",

abstract = "Changes in antibody glycosylation are linked to inflammation across several diseases. Alterations in bulk antibody galactosylation can predict rheumatic flares, act as a sensor for immune activation, predict gastric cancer relapse, track with biological age, shift with vaccination, change with HIV reservoir size on therapy, and decrease in HIV and HCV infections. However, whether changes in antibody Fc biology also track with reservoir rebound time remains unclear. The identification of a biomarker that could forecast viral rebound time could significantly accelerate the downselection and iterative improvement of promising HIV viral eradication strategies. Using a comprehensive antibody Fc-profiling approach, the level of HIV-specific antibody Fc N-galactosylation is significantly associated with time to rebound after treatment discontinuation across three independent cohorts. Thus virus-specific antibody glycosylation may represent a promising, simply measured marker to track reservoir reactivation.",

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author = "Rasmus Offersen and Yu, {Wen Han} and Scully, {Eileen P.} and Boris Julg and Zelda Euler and Saheli Sadanand and Dario Garcia-Dominguez and Lu Zheng and Rasmussen, {Thomas A.} and Jennewein, {Madeleine F.} and Caitlyn Linde and Jessica Sassic and Giuseppe Lofano and Selena Vigano and Stephenson, {Kathryn E.} and Stephanie Fischinger and Suscovich, {Todd J.} and Mathias Lichterfeld and Douglas Lauffenburger and Rosenberg, {Erik S.} and Todd Allen and Marcus Altfeld and Charles, {Richelle C.} and Lars {\O}stergaard and Martin Tolstrup and Barouch, {Dan H.} and S{\o}gaard, {Ole S.} and Galit Alter",

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doi = "10.1016/j.celrep.2020.108502",

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AU - Offersen, Rasmus

AU - Yu, Wen Han

AU - Scully, Eileen P.

AU - Julg, Boris

AU - Euler, Zelda

AU - Sadanand, Saheli

AU - Garcia-Dominguez, Dario

AU - Zheng, Lu

AU - Rasmussen, Thomas A.

AU - Jennewein, Madeleine F.

AU - Linde, Caitlyn

AU - Sassic, Jessica

AU - Lofano, Giuseppe

AU - Vigano, Selena

AU - Stephenson, Kathryn E.

AU - Fischinger, Stephanie

AU - Suscovich, Todd J.

AU - Lichterfeld, Mathias

AU - Lauffenburger, Douglas

AU - Rosenberg, Erik S.

AU - Allen, Todd

AU - Altfeld, Marcus

AU - Charles, Richelle C.

AU - Østergaard, Lars

AU - Tolstrup, Martin

AU - Barouch, Dan H.

AU - Søgaard, Ole S.

AU - Alter, Galit

PY - 2020/12/15

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N2 - Changes in antibody glycosylation are linked to inflammation across several diseases. Alterations in bulk antibody galactosylation can predict rheumatic flares, act as a sensor for immune activation, predict gastric cancer relapse, track with biological age, shift with vaccination, change with HIV reservoir size on therapy, and decrease in HIV and HCV infections. However, whether changes in antibody Fc biology also track with reservoir rebound time remains unclear. The identification of a biomarker that could forecast viral rebound time could significantly accelerate the downselection and iterative improvement of promising HIV viral eradication strategies. Using a comprehensive antibody Fc-profiling approach, the level of HIV-specific antibody Fc N-galactosylation is significantly associated with time to rebound after treatment discontinuation across three independent cohorts. Thus virus-specific antibody glycosylation may represent a promising, simply measured marker to track reservoir reactivation.

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KW - B cells

KW - Fc-receptors

KW - HIV

KW - HIV remission

KW - HIV reservoir

KW - antibodies

KW - biomarkers

KW - cure

KW - glycosylation

KW - viral host response

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HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound

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Keywords

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