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Superimmunity by pan-sarbecovirus nanobodies.
Xiang, Yufei; Huang, Wei; Liu, Hejun; Sang, Zhe; Nambulli, Sham; Tubiana, Jérôme; Williams, Kevin L; Duprex, W Paul; Schneidman-Duhovny, Dina; Wilson, Ian A; Taylor, Derek J; Shi, Yi.
  • Xiang Y; Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Huang W; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA.
  • Liu H; Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA 92037, USA.
  • Sang Z; The University of Pittsburgh and Carnegie Mellon University Program for Computational Biology, Pittsburgh, PA 15213, USA.
  • Nambulli S; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Tubiana J; School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel; Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel.
  • Williams KL; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Duprex WP; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Schneidman-Duhovny D; School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
  • Wilson IA; Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, Scripps Research, La Jolla, CA 92037, USA.
  • Taylor DJ; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA.
  • Shi Y; Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA; The University of Pittsburgh and Carnegie Mellon University Program for Computational Biology, Pittsburgh, PA 15213, USA; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 100
Cell Rep ; 39(13): 111004, 2022 06 28.
Article in English | MEDLINE | ID: covidwho-1944462
ABSTRACT
Vaccine boosters and infection can facilitate the development of SARS-CoV-2 antibodies with improved potency and breadth. Here, we observe superimmunity in a camelid extensively immunized with the SARS-CoV-2 receptor-binding domain (RBD). We rapidly isolate a large repertoire of specific ultra-high-affinity nanobodies that bind strongly to all known sarbecovirus clades using integrative proteomics. These pan-sarbecovirus nanobodies (psNbs) are highly effective against SARS-CoV and SARS-CoV-2 variants, including Omicron, with the best median neutralization potency at single-digit nanograms per milliliter. A highly potent, inhalable, and bispecific psNb (PiN-31) is also developed. Structural determinations of 13 psNbs with the SARS-CoV-2 spike or RBD reveal five epitope classes, providing insights into the mechanisms and evolution of their broad activities. The highly evolved psNbs target small, flat, and flexible epitopes that contain over 75% of conserved RBD surface residues. Their potencies are strongly and negatively correlated with the distance of the epitopes from the receptor binding sites.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severe acute respiratory syndrome-related coronavirus / Single-Domain Antibodies / COVID-19 Topics: Vaccines / Variants Limits: Humans Language: English Journal: Cell Rep Year: 2022 Document Type: Article Affiliation country: J.celrep.2022.111004

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severe acute respiratory syndrome-related coronavirus / Single-Domain Antibodies / COVID-19 Topics: Vaccines / Variants Limits: Humans Language: English Journal: Cell Rep Year: 2022 Document Type: Article Affiliation country: J.celrep.2022.111004