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Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses.
Ray, Rashmi; Nait Mohamed, Faez Amokrane; Maurer, Daniel P; Huang, Jiachen; Alpay, Berk A; Ronsard, Larance; Xie, Zhenfei; Han, Julianna; Fernandez-Quintero, Monica; Phan, Quynh Anh; Ursin, Rebecca L; Vu, Mya; Kirsch, Kathrin H; Prum, Thavaleak; Rosado, Victoria C; Bracamonte-Moreno, Thalia; Okonkwo, Vintus; Bals, Julia; McCarthy, Caitlin; Nair, Usha; Kanekiyo, Masaru; Ward, Andrew B; Schmidt, Aaron G; Batista, Facundo D; Lingwood, Daniel.
Afiliação
  • Ray R; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Nait Mohamed FA; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA. Electronic address: fnaitmohamed@mgh.harvard.edu.
  • Maurer DP; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Huang J; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Alpay BA; Systems, Synthetic, and Quantitative Biology Program, Harvard University, Cambridge, MA 02138, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
  • Ronsard L; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Xie Z; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Han J; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Fernandez-Quintero M; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of General, Inorganic and Theoretical Chemistry, Center for Chemistry and Biomedicine, University of Innsbruck, Innrain 80-82/III, 6020 Innsbruck, Austria.
  • Phan QA; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Ursin RL; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Vu M; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Kirsch KH; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Prum T; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Rosado VC; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Bracamonte-Moreno T; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Okonkwo V; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Bals J; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • McCarthy C; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Nair U; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
  • Kanekiyo M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892-3005, USA.
  • Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Schmidt AG; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: aschmidt@crystal.harvard.edu.
  • Batista FD; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; Department of Biology, The Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: fbatista1@mgh.harvard.edu.
  • Lingwood D; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA. Electronic address: dlingwood@mgh.harvard.edu.
Immunity ; 57(5): 1141-1159.e11, 2024 May 14.
Article em En | MEDLINE | ID: mdl-38670113
ABSTRACT
Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, intergroup protective bnAbs can be generated by human antibody paratopes that accommodate the conserved glycan differences between the group 1 and group 2 stems. We applied germline-engaging nanoparticle immunogens to elicit a class of cross-group bnAbs from physiological precursor frequency within a humanized mouse model. Cross-group protection depended on the presence of the human bnAb precursors within the B cell repertoire, and the vaccine-expanded antibodies enriched for an N55T substitution in the CDRH2 loop, a hallmark of the bnAb class. Structurally, this single mutation introduced a flexible fulcrum to accommodate glycosylation differences and could alone enable cross-group protection. Thus, broad IAV immunity can be expanded from the germline repertoire via minimal antigenic input and an exceptionally simple antibody development pathway.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Vírus da Influenza A / Vacinas contra Influenza / Vacinação / Infecções por Orthomyxoviridae / Anticorpos Neutralizantes / Anticorpos Antivirais Limite: Animals / Humans Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Vírus da Influenza A / Vacinas contra Influenza / Vacinação / Infecções por Orthomyxoviridae / Anticorpos Neutralizantes / Anticorpos Antivirais Limite: Animals / Humans Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos