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Glycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses.
Boyoglu-Barnum, Seyhan; Hutchinson, Geoffrey B; Boyington, Jeffrey C; Moin, Syed M; Gillespie, Rebecca A; Tsybovsky, Yaroslav; Stephens, Tyler; Vaile, John R; Lederhofer, Julia; Corbett, Kizzmekia S; Fisher, Brian E; Yassine, Hadi M; Andrews, Sarah F; Crank, Michelle C; McDermott, Adrian B; Mascola, John R; Graham, Barney S; Kanekiyo, Masaru.
Afiliação
  • Boyoglu-Barnum S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA.
  • Hutchinson GB; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA.
  • Boyington JC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA.
  • Moin SM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA.
  • Gillespie RA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA.
  • Tsybovsky Y; 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.
  • Stephens T; 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.
  • Vaile JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA.
  • Lederhofer J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA.
  • Corbett KS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA.
  • Fisher BE; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA.
  • Yassine HM; Biomedical Research Center, Qatar University, New Research Complex Zone 5, Doha, Qatar.
  • Andrews SF; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA.
  • Crank MC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA.
  • McDermott AB; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA.
  • Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA.
  • Graham BS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA. bgraham@nih.gov.
  • Kanekiyo M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD, 20892, USA. kanekiyom@nih.gov.
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polissacarídeos / Vacinas contra Influenza / Glicoproteínas de Hemaglutininação de Vírus da Influenza / Nanopartículas Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polissacarídeos / Vacinas contra Influenza / Glicoproteínas de Hemaglutininação de Vírus da Influenza / Nanopartículas Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article