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Rationally designed immunogens enable immune focusing following SARS-CoV-2 spike imprinting.
Hauser, Blake M; Sangesland, Maya; St Denis, Kerri J; Lam, Evan C; Case, James Brett; Windsor, Ian W; Feldman, Jared; Caradonna, Timothy M; Kannegieter, Ty; Diamond, Michael S; Balazs, Alejandro B; Lingwood, Daniel; Schmidt, Aaron G.
  • Hauser BM; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Sangesland M; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • St Denis KJ; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Lam EC; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Case JB; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Windsor IW; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Laboratory of Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
  • Feldman J; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Caradonna TM; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Kannegieter T; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Diamond MS; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 6311
  • Balazs AB; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Lingwood D; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Schmidt AG; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: aschmidt@crystal.harvard.edu.
Cell Rep ; 38(12): 110561, 2022 03 22.
Article in English | MEDLINE | ID: covidwho-1797095
ABSTRACT
Eliciting antibodies to surface-exposed viral glycoproteins can generate protective responses that control and prevent future infections. Targeting conserved sites may reduce the likelihood of viral escape and limit the spread of related viruses with pandemic potential. Here we leverage rational immunogen design to focus humoral responses on conserved epitopes. Using glycan engineering and epitope scaffolding in boosting immunogens, we focus murine serum antibody responses to conserved receptor binding motif (RBM) and receptor binding domain (RBD) epitopes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike imprinting. Although all engineered immunogens elicit a robust SARS-CoV-2-neutralizing serum response, RBM-focusing immunogens exhibit increased potency against related sarbecoviruses, SARS-CoV, WIV1-CoV, RaTG13-CoV, and SHC014-CoV; structural characterization of representative antibodies defines a conserved epitope. RBM-focused sera confer protection against SARS-CoV-2 challenge. Thus, RBM focusing is a promising strategy to elicit breadth across emerging sarbecoviruses without compromising SARS-CoV-2 protection. These engineering strategies are adaptable to other viral glycoproteins for targeting conserved epitopes.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Envelope Proteins / COVID-19 Limits: Animals Language: English Journal: Cell Rep Year: 2022 Document Type: Article Affiliation country: J.celrep.2022.110561

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Envelope Proteins / COVID-19 Limits: Animals Language: English Journal: Cell Rep Year: 2022 Document Type: Article Affiliation country: J.celrep.2022.110561