Glycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses

Seyhan 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 () and Masaru Kanekiyo ()
Additional contact information
Seyhan Boyoglu-Barnum: National Institutes of Health
Geoffrey B. Hutchinson: National Institutes of Health
Jeffrey C. Boyington: National Institutes of Health
Syed M. Moin: National Institutes of Health
Rebecca A. Gillespie: National Institutes of Health
Yaroslav Tsybovsky: Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, ATRF
Tyler Stephens: Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, ATRF
John R. Vaile: National Institutes of Health
Julia Lederhofer: National Institutes of Health
Kizzmekia S. Corbett: National Institutes of Health
Brian E. Fisher: National Institutes of Health
Hadi M. Yassine: Qatar University
Sarah F. Andrews: National Institutes of Health
Michelle C. Crank: National Institutes of Health
Adrian B. McDermott: National Institutes of Health
John R. Mascola: National Institutes of Health
Barney S. Graham: National Institutes of Health
Masaru Kanekiyo: National Institutes of Health

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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 Asn38HA1 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 N38HA1 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.

Date: 2020
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DOI: 10.1038/s41467-020-14579-4

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