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

Cell Rep. 2020 Dec 15;33(11):108502. doi: 10.1016/j.celrep.2020.108502.

Authors

Rasmus Offersen¹, Wen-Han Yu², Eileen P Scully³, Boris Julg⁴, Zelda Euler⁴, Saheli Sadanand⁴, Dario Garcia-Dominguez⁴, Lu Zheng⁵, Thomas A Rasmussen⁶, Madeleine F Jennewein⁴, Caitlyn Linde⁴, Jessica Sassic⁴, Giuseppe Lofano⁴, Selena Vigano⁴, Kathryn E Stephenson⁷, Stephanie Fischinger⁴, Todd J Suscovich⁴, Mathias Lichterfeld⁸, Douglas Lauffenburger⁹, Erik S Rosenberg¹⁰, Todd Allen⁴, Marcus Altfeld¹¹, Richelle C Charles¹⁰, Lars Østergaard¹², Martin Tolstrup¹², Dan H Barouch¹³, Ole S Søgaard¹², Galit Alter¹⁴

Affiliations

¹ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Infectious Diseases, Aarhus University Hospital, Aarhus 8000, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus 8000, Denmark.
² Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
³ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁴ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
⁵ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
⁶ Department of Infectious Diseases, Aarhus University Hospital, Aarhus 8000, Denmark.
⁷ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
⁸ Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA 02115, USA.
⁹ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
¹⁰ Division of Infectious Disease, Massachusetts General Hospital, Boston, MA 02114, USA.
¹¹ Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
¹² Department of Infectious Diseases, Aarhus University Hospital, Aarhus 8000, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus 8000, Denmark.
¹³ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
¹⁴ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: galter@mgh.harvard.edu.

PMID: 33326789
DOI: 10.1016/j.celrep.2020.108502

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.

Keywords: B cells; Fc-receptors; HIV; HIV remission; HIV reservoir; antibodies; biomarkers; cure; glycosylation; viral host response.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Glycosylation
HIV Antibodies / metabolism*
Humans
Viral Load / methods*

Substances

HIV Antibodies