tetano
Editor, Senior Moderator
Nat Commun. 2020 Feb 7;11(1):791. doi: 10.1038/s41467-020-14579-4. [h=1]Glycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses.[/h]
Boyoglu-Barnum S[SUP]1[/SUP], Hutchinson GB[SUP]1[/SUP], Boyington JC[SUP]1[/SUP], Moin SM[SUP]1[/SUP], Gillespie RA[SUP]1[/SUP], Tsybovsky Y[SUP]2[/SUP], Stephens T[SUP]2[/SUP], Vaile JR[SUP]1[/SUP], Lederhofer J[SUP]1[/SUP], Corbett KS[SUP]1[/SUP], Fisher BE[SUP]1[/SUP], Yassine HM[SUP]3[/SUP], Andrews SF[SUP]1[/SUP], Crank MC[SUP]1[/SUP], McDermott AB[SUP]1[/SUP], Mascola JR[SUP]1[/SUP], Graham BS[SUP]4[/SUP], Kanekiyo M[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUB]HA1[/SUB] 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[SUB]HA1[/SUB] 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.
PMID: 32034141 PMCID: PMC7005838 DOI: 10.1038/s41467-020-14579-4
Free PMC Article
Boyoglu-Barnum S[SUP]1[/SUP], Hutchinson GB[SUP]1[/SUP], Boyington JC[SUP]1[/SUP], Moin SM[SUP]1[/SUP], Gillespie RA[SUP]1[/SUP], Tsybovsky Y[SUP]2[/SUP], Stephens T[SUP]2[/SUP], Vaile JR[SUP]1[/SUP], Lederhofer J[SUP]1[/SUP], Corbett KS[SUP]1[/SUP], Fisher BE[SUP]1[/SUP], Yassine HM[SUP]3[/SUP], Andrews SF[SUP]1[/SUP], Crank MC[SUP]1[/SUP], McDermott AB[SUP]1[/SUP], Mascola JR[SUP]1[/SUP], Graham BS[SUP]4[/SUP], Kanekiyo M[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUB]HA1[/SUB] 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[SUB]HA1[/SUB] 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.
PMID: 32034141 PMCID: PMC7005838 DOI: 10.1038/s41467-020-14579-4
Free PMC Article