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Engaging an HIV vaccine target through the acquisition of low B cell affinity.
Ronsard, Larance; Yousif, Ashraf S; Nait Mohamed, Faez Amokrane; Feldman, Jared; Okonkwo, Vintus; McCarthy, Caitlin; Schnabel, Julia; Caradonna, Timothy; Barnes, Ralston M; Rohrer, Daniel; Lonberg, Nils; Schmidt, Aaron; Lingwood, Daniel.
Afiliação
  • Ronsard L; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA, 02139, USA.
  • Yousif AS; 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.
  • Feldman J; 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.
  • McCarthy C; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA, 02139, USA.
  • Schnabel J; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA, 02139, USA.
  • Caradonna T; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA, 02139, USA.
  • Barnes RM; Bristol-Myers Squibb, 700 Bay Rd, Redwood City, CA, 94063-2478, USA.
  • Rohrer D; Bristol-Myers Squibb, 700 Bay Rd, Redwood City, CA, 94063-2478, USA.
  • Lonberg N; Bristol-Myers Squibb, 700 Bay Rd, Redwood City, CA, 94063-2478, USA.
  • Schmidt A; The Ragon Institute of Mass General, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA, 02139, USA.
  • Lingwood D; Department of Microbiology, Harvard Medical School, Boston, MA, 02115, USA.
Nat Commun ; 14(1): 5249, 2023 08 28.
Article em En | MEDLINE | ID: mdl-37640732
ABSTRACT
Low affinity is common for germline B cell receptors (BCR) seeding development of broadly neutralizing antibodies (bnAbs) that engage hypervariable viruses, including HIV. Antibody affinity selection is also non-homogenizing, insuring the survival of low affinity B cell clones. To explore whether this provides a natural window for expanding human B cell lineages against conserved vaccine targets, we deploy transgenic mice mimicking human antibody diversity and somatic hypermutation (SHM) and immunize with simple monomeric HIV glycoprotein envelope immunogens. We report an immunization regimen that focuses B cell memory upon the conserved CD4 binding site (CD4bs) through both conventional affinity maturation and reproducible expansion of low affinity BCR clones with public patterns in SHM. In the latter instance, SHM facilitates target acquisition by decreasing binding strength. This suggests that permissive B cell selection enables the discovery of antibody epitopes, in this case an HIV bnAb site.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por HIV / Vacinas contra a AIDS Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por HIV / Vacinas contra a AIDS Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article