Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA.
Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, ATRF, 8560 Progressive Drive, Frederick, MD, 21702, USA.
Nat Commun. 2020 Feb 7;11(1):791. doi: 10.1038/s41467-020-14579-4.
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.
保守的血凝素（HA）茎一直是通用流感疫苗研究的重点。已经证明，甲型流感组 1 HA 茎纳米颗粒在动物中提供了异源保护；然而，这种保护并不能扩展到组 2 病毒，部分原因是组 1 和 2 茎之间的糖基化差异。在这里，我们展示了在基于 A/New Caledonia/20/99（H1N1）的组 1 茎纳米颗粒（gN38 变体）上引入组 2 聚糖在 Asn38，从而扩大了与组 2 HAs 交叉反应的抗体反应。由 gN38 变体引发的免疫球蛋白提供了针对组 2 H7N9 病毒感染的完全保护，而该变体失去了对组 1 H5N1 病毒的保护。因此，N38 聚糖在控制对群体决定茎表位的可及性方面对于指导抗体反应至关重要。通过糖基重定位将针对茎的抗体反应精确靶向到脆弱部位可能是实现跨组流感保护的一步。
