Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination

PLoS Pathogens

Don Francis¹  Maria Pau²  Hanneke Schuitemaker²  Dan H. Barouch³  Patricia Fast⁴  Bruce D. Walker⁵  Dagna Laufer⁵  Hendrik Streeck⁶  Galit Alter⁷  Lindsey Baden⁷  Amy W. Chung⁷  Todd Suscovich⁷  Alison E. Mahan⁷  Madeleine F. Jennewein⁷  Kendall Dionne⁷  Jacquelynne Tedesco⁷ 

[1] Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands;Crucell, Leiden, Netherlands;Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America;Global Solutions for Infectious Diseases, South San Francisco, California, United States of America;International AIDS Vaccine Initiative, New York, New York, United States of America;Military HIV Research Program, Walter Reed Medical Research Institute, Bethesda, Maryland, United States of America;Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, United States of America

关键词: Antibodies;    Glycosylation;    Inflammation;    HIV;    Vaccines;    Vaccination;    immunization;    Antigens;    Principal component analysis;   

DOI  :  10.1371/journal.ppat.1005456

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.  

【 授权许可】

CC BY