Editors' ChoiceVaccine Design

Improving Immunity to Flu

See allHide authors and affiliations

Science Translational Medicine  04 Nov 2009:
Vol. 1, Issue 5, pp. 5ec20
DOI: 10.1126/scitranslmed.3000548

Fears of a catastrophic influenza pandemic have been fanned by outbreaks of the highly pathogenic H5N1 "bird flu" and by the spread of the pandemic H1N1/09 virus. A full understanding of viral transmission requires characterization of the viral protein hemagglutinin (HA). This integral membrane protein coats the surface of the virus and is responsible for its attachment to specific sialic acid–containing receptors on host respiratory cells, which allows viral entry. HA is glycosylated, and glycan groups at certain positions affect virus function. One type of flu virus (H3N2) has gained potential glycosylation sites over the last 40 years, and its increased glycosylation is associated with decreased virulence. However, little is known about how these short chains of sugars affect the ability of HA to bind the host's receptor or to elicit an immune response. To address these issues, Wang et al. prepared four distinctly glycosylated HA variants and studied the binding of these variants, which appeared to retain normal structure, to analogs of the HA-binding ligand. The researchers found that shortening the glycan structures increased the binding affinity, but decreased binding specificity, for sialic acid ligands. Antibodies raised against the HA variant that carried only a single monosaccharide (N-acetylglucosamine) at each glycosylation site bound with higher affinity to H5 and H1 viral subtypes than did antibodies raised against fully glycosylated HA—and provided substantially more protection against a lethal dose of H5N1 virus in mice. Thus, removing glycans from viral glycoproteins might be a useful approach to vaccine design.

C.-C. Wang et al., Glycans on influenza hemagglutinin affect receptor binding and immune response. Proc. Natl. Acad. Sci. U.S.A. 106, 18137–18142 (2009). [Abstract]

Navigate This Article