title: Natural variation in Fc glycosylation of HIV-specific antibodies impacts antiviral activity.
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 agalactosylated 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 glycosyltransferases 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.
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Ackerman
authors.forename: Max
authors.initials: M
authors.lastname: Crispin
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Yu
authors.forename: Kavitha
authors.initials: K
authors.lastname: Baruah
authors.forename: Austin W
authors.initials: AW
authors.lastname: Boesch
authors.forename: David J
authors.initials: DJ
authors.lastname: Harvey
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Dugast
authors.forename: Erin L
authors.initials: EL
authors.lastname: Heizen
authors.forename: Altan
authors.initials: A
authors.lastname: Ercan
authors.forename: Ickwon
authors.initials: I
authors.lastname: Choi
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
authors.forename: Peter A
authors.initials: PA
authors.lastname: Nigrovic
authors.forename: Chris
authors.initials: C
authors.lastname: Bailey-Kellogg
authors.forename: Chris
authors.initials: C
authors.lastname: Scanlan
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
mesh_terms: D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006031:Glycosylation; D015483:HIV Antibodies / Q000737:chemistry / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000276:immunology*; D007074:Immunoglobulin G / Q000737:chemistry; D013058:Mass Spectrometry; D011134:Polysaccharides / Q000737:chemistry; D020033:Protein Isoforms / Q000737:chemistry; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D015483:HIV Antibodies; D015488:HIV Antigens; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011134:Polysaccharides; D020033:Protein Isoforms
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