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Graphical Abstract
Highlights
Glycosylation is not currently considered in flu vaccine design.
Glycosylation influences on immunodominance are not well understood.
Identification of site-specific glycosylation using mass spectrometry has matured.
New methods are needed to quantify site-specific glycosylation for vaccine design.
Abstract
Low vaccine efficacy against seasonal influenza A virus (IAV) stems from the ability of the virus to evade existing immunity while maintaining fitness. Although most potent neutralizing antibodies bind antigenic sites on the globular head domain of the IAV envelope glycoprotein hemagglutinin (HA), the error-prone IAV polymerase enables rapid evolution of key antigenic sites, resulting in immune escape. Significantly, the appearance of new N-glycosylation consensus sequences (sequons, NXT/NXS, rarely NXC) on the HA globular domain occurs among the more prevalent mutations as an IAV strain undergoes antigenic drift. The appearance of new glycosylation shields underlying amino acid residues from antibody contact, tunes receptor specificity, and balances receptor avidity with virion escape, all of which help maintain viral propagation through seasonal mutations. The World Health Organization selects seasonal vaccine strains based on information from surveillance, laboratory, and clinical observations. Although the genetic sequences are known, mature glycosylated structures of circulating strains are not defined. In this review, we summarize mass spectrometric methods for quantifying site-specific glycosylation in IAV strains and compare the evolution of IAV glycosylation to that of human immunodeficiency virus. We argue that the determination of site-specific glycosylation of IAV glycoproteins would enable development of vaccines that take advantage of glycosylation-dependent mechanisms whereby virus glycoproteins are processed by antigen presenting cells.
Footnotes
Author contributions: D.C. and J.Z. wrote the paper.
↵* This work is supported by NIH grant U01CA221234 and the Graduate Medical Sciences program at Boston University School of Medicine. No author has an actual or perceived conflict of interest with the contents of this article.
- Received April 8, 2019.
- Revision received August 18, 2019.
- © 2019 Chang and Zaia.
Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.