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

By Seyhan Boyoglu-Barnum, Geoffrey B. Hutchinson, J. Boyington, Syed M. Moin, Rebecca A. Gillespie, Y. Tsybovsky, T. Stephens, John R. Vaile, Julia Lederhofer, Kizzmekia S. Corbett and 8 more. 2020

50 citations recorded by the source corpus.

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. Influenza virus hemagglutinin (HA) stem between group 1 and 2 viruses has different glycosylation patterns, likely hampering cross-group protection. Here, Boyoglu-Barnum et al. show that introducing a group 2 glycan into a group 1 stem nanoparticle vaccine broadens antibody responses in mice to cross-react with group 2 HAs.

Subfields: Epidemiology, Infectious Diseases

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Citations in the corpus

• A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection (2022, background): “Current influenza vaccines provide protection primarily through the induction of neutralizing antibodies against the immunodominant globular head region of the HA which undergoes continuous antigenic drift, and hence, is highly variable among different isolates [6].”