IgG anti-HA Fc glycoform modulation is predictive of influenza vaccine efficacy (IRC10P.412)

阅读量:

20

作者:

T WangJ MaamaryS SchlesingerJ Ravetch

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摘要:

Protective anti-viral vaccines elicit high affinity, antigen-specific neutralizing antibodies through secondary diversification mechanisms involving the selection of B cells bearing somatically hypermutated B cell antigen receptors in the germinal center. This selection process involves the interaction of the B cell receptor with antigen retained in the form of immune complexes, thus dictating that Fc-Fc receptor (FcR) interactions contribute to the selection process. FcRs are diverse in function and can transduce immunomodulatory, activating, or inhibitory signaling depending on which receptor(s) are engaged; the sum of these activities contributes to the generation of protective IgGs through mechanisms including efficient antigen presentation and dendritic cell maturation as well as directing B cell activation and selection. Immune complex-FcR interactions are governed by the precise structure of Fc domains within an immune complex, which, in turn, depends on the subclass distribution and Fc glycan composition of antigen-specific serum IgG. We performed the first detailed structural analysis of IgG Fc domains following influenza virus vaccination and found complex regulation of both subclass and Fc glycoforms. The abundance of sialylated Fc glycans on HA-specific IgG was found to predict the quality of vaccine response suggesting a mechanism by which sFc glycans modulate B cell activation thresholds, thereby driving the production of neutralizing, high affinity IgGs.

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被引量:

7

年份:

2015

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