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Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination.

Authors :
Mahan AE
Jennewein MF
Suscovich T
Dionne K
Tedesco J
Chung AW
Streeck H
Pau M
Schuitemaker H
Francis D
Fast P
Laufer D
Walker BD
Baden L
Barouch DH
Alter G
Source :
PLoS pathogens [PLoS Pathog] 2016 Mar 16; Vol. 12 (3), pp. e1005456. Date of Electronic Publication: 2016 Mar 16 (Print Publication: 2016).
Publication Year :
2016

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.  .

Details

Language :
English
ISSN :
1553-7374
Volume :
12
Issue :
3
Database :
MEDLINE
Journal :
PLoS pathogens
Publication Type :
Academic Journal
Accession number :
26982805
Full Text :
https://doi.org/10.1371/journal.ppat.1005456