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AuthorBoyoglu-Barnum, Seyhan
AuthorHutchinson, Geoffrey B
AuthorBoyington, Jeffrey C
AuthorMoin, Syed M
AuthorGillespie, Rebecca A
AuthorTsybovsky, Yaroslav
AuthorStephens, Tyler
AuthorVaile, John R
AuthorLederhofer, Julia
AuthorCorbett, Kizzmekia S
AuthorFisher, Brian E
AuthorYassine, Hadi M
AuthorAndrews, Sarah F
AuthorCrank, Michelle C
AuthorMcDermott, Adrian B
AuthorMascola, John R
AuthorGraham, Barney S
AuthorKanekiyo, Masaru
Available date2020-08-30T05:29:37Z
Publication Date2020-02-07
Publication NameNature Communications
Identifierhttp://dx.doi.org/10.1038/s41467-020-14579-4
CitationBoyoglu-Barnum, S., Hutchinson, G.B., Boyington, J.C. et al. Glycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses. Nat Commun 11, 791 (2020). https://doi.org/10.1038/s41467-020-14579-4
URIhttp://hdl.handle.net/10576/15855
AbstractThe conserved hemagglutinin (HA) stem has been a focus of universal influenza vaccine efforts. Influenza A group 1 HA stem-nanoparticles have been demonstrated to confer heterosubtypic protection in animals; however, the protection does not extend to group 2 viruses, due in part to differences in glycosylation between group 1 and 2 stems. Here, we show that introducing the group 2 glycan at Asn38 to a group 1 stem-nanoparticle (gN38 variant) based on A/New Caledonia/20/99 (H1N1) broadens antibody responses to cross-react with group 2 HAs. Immunoglobulins elicited by the gN38 variant provide complete protection against group 2 H7N9 virus infection, while the variant loses protection against a group 1 H5N1 virus. The N38 glycan thus is pivotal in directing antibody responses by controlling access to group-determining stem epitopes. Precise targeting of stem-directed antibody responses to the site of vulnerability by glycan repositioning may be a step towards achieving cross-group influenza protection.
SponsorWe thank D. Scorpio, A. Taylor, H. Bao, C. Chiedi, M. Dillon, L. Gilliam, and G. Sarbador (VRC) for help with animal studies; H. Andersen (Bioqual, Inc.) for mouse challenge studies; C. Case (Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.) for help with challenge study coordination; A. Kumar (VRC) for producing RSV proteins; and members of Viral Pathogenesis Laboratory and Universal Influenza Vaccine Program (VRC) for helpful discussion. Support for this work was provided by the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Electron microscopy data collection and analyses were funded by federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract number HHSN261200800001E, and by Leidos Biomedical Research, Inc. (Y.T. and T.S.).
Languageen
PublisherNature Research
SubjectGlycoproteins
Humoral immunity
Influenza virus
Vaccines
TitleGlycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses.
TypeArticle
Issue Number2
Volume Number11
ESSN2041-1723
dc.accessType Open Access


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