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TitleGlycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses.
Journal, issue, pagesNat Commun, Vol. 11, Issue 1, Page 791, Year 2020
Publish dateFeb 7, 2020
AuthorsSeyhan Boyoglu-Barnum / Geoffrey B Hutchinson / Jeffrey C Boyington / Syed M Moin / Rebecca A Gillespie / Yaroslav Tsybovsky / Tyler Stephens / John R Vaile / Julia Lederhofer / Kizzmekia S Corbett / Brian E Fisher / Hadi M Yassine / Sarah F Andrews / Michelle C Crank / Adrian B McDermott / John R Mascola / Barney S Graham / Masaru Kanekiyo /
PubMed 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 ...The 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.
External linksNat Commun / PubMed:32034141 / PubMed Central
MethodsEM (single particle)
Resolution4.7 - 6.4 Å
Structure data

EMDB-20911:
Group 1 H1 influenza stem nanoparticle with a group 2-like N-linked glycosylation site at position 38
Method: EM (single particle) / Resolution: 4.7 Å

EMDB-20912:
Group 1 H1 influenza stem nanoparticle with an H38R mutation
Method: EM (single particle) / Resolution: 6.4 Å

EMDB-20913:
Group 1 H1 influenza stem nanoparticle
Method: EM (single particle) / Resolution: 6.3 Å

Source
  • Influenza A virus

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