Glycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses.
Nat Commun
; 11(1): 791, 2020 02 07.
Article
em En
| MEDLINE
| ID: mdl-32034141
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
Base de dados:
MEDLINE
Assunto principal:
Polissacarídeos
/
Vacinas contra Influenza
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Glicoproteínas de Hemaglutininação de Vírus da Influenza
/
Nanopartículas
Limite:
Animals
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2020
Tipo de documento:
Article