PMID: 26982805
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.  .
Date: 1970-08-22
Year: 2016
Journal: PLoS Pathog.
PMID Author: 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
PMC Link #: PMC4794126
Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination. PLoS Pathog. 2016;12(3):e1005456 doi: 10.1371/journal.ppat.1005456

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