title: Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination.
abstract: Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain (Fc domain) regulate antibody functionality: changes in antibody subclass and changes in a single N-linked glycan located in the CH2 domain of the IgG Fc. Together, these modifications provide a specific set of instructions to the innate immune system to direct the elimination of antibody-bound antigens. While it is clear that subclass selection is actively regulated during the course of natural infection, it is unclear whether antibody glycosylation can be tuned, in a signal-specific or pathogen-specific manner. Here, we show that antibody glycosylation is determined in an antigen- and pathogen-specific manner during HIV infection. Moreover, while dramatic differences exist in bulk IgG glycosylation among individuals in distinct geographical locations, immunization is able to overcome these differences and elicit antigen-specific antibodies with similar antibody glycosylation patterns. Additionally, distinct vaccine regimens induced different antigen-specific IgG glycosylation profiles, suggesting that antibody glycosylation is not only programmable but can be manipulated via the delivery of distinct inflammatory signals during B cell priming. These data strongly suggest that the immune system naturally drives antibody glycosylation in an antigen-specific manner and highlights a promising means by which next-generation therapeutics and vaccines can harness the antiviral activity of the innate immune system via directed alterations in antibody glycosylation in vivo.  .
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Alison E
authors.initials: AE
authors.lastname: Mahan
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Madeleine F
authors.initials: MF
authors.lastname: Jennewein
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Todd
authors.initials: T
authors.lastname: Suscovich
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Kendall
authors.initials: K
authors.lastname: Dionne
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Jacquelynne
authors.initials: J
authors.lastname: Tedesco
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Amy W
authors.initials: AW
authors.lastname: Chung
authors.affiliation: Military HIV Research Program, Walter Reed Medical Research Institute, Bethesda, Maryland, United States of America.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
authors.affiliation: Crucell, Leiden, Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Pau
authors.affiliation: Crucell, Leiden, Netherlands.|Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.affiliation: Global Solutions for Infectious Diseases, South San Francisco, California, United States of America.
authors.forename: Don
authors.initials: D
authors.lastname: Francis
authors.affiliation: International AIDS Vaccine Initiative, New York, New York, United States of America.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fast
authors.affiliation: International AIDS Vaccine Initiative, New York, New York, United States of America.
authors.forename: Dagna
authors.initials: D
authors.lastname: Laufer
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Baden
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.|Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006031:Glycosylation; D015483:HIV Antibodies / Q000276:immunology* / Q000302:isolation & purification; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006679:HIV Seropositivity; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007074:Immunoglobulin G; D008297:Male; D010587:Phagocytosis; D014611:Vaccination; D006023:Glycoproteins
chemical_list: D015483:HIV Antibodies; D015488:HIV Antigens; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; C046179:glycosylated IgG; D006023:Glycoproteins