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Ultrapotent and broad neutralization of SARS-CoV-2 variants by modular, tetravalent, bi-paratopic antibodies.
Miersch, Shane; Sharma, Nitin; Saberianfar, Reza; Chen, Chao; Caccuri, Francesca; Zani, Alberto; Caruso, Arnaldo; Case, James Brett; Diamond, Michael S; Amarasinghe, Gaya K; Novelli, Giuseppe; Sidhu, Sachdev S.
  • Miersch S; The Donnelly Centre, University of Toronto, Toronto, ON, Canada. Electronic address: shane.miersch@utoronto.ca.
  • Sharma N; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  • Saberianfar R; The Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • Chen C; The Donnelly Centre, University of Toronto, Toronto, ON, Canada.
  • Caccuri F; Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia Medical School, 25123 Brescia, Italy.
  • Zani A; Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia Medical School, 25123 Brescia, Italy.
  • Caruso A; Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia Medical School, 25123 Brescia, Italy.
  • Case JB; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Diamond MS; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Andrew M. an
  • Amarasinghe GK; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  • Novelli G; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; IRCCS Neuromed, Pozzilli, Isernia, Italy; Department of Pharmacology, School of Medicine, University of Nevada, Reno, NV, USA.
  • Sidhu SS; The Donnelly Centre, University of Toronto, Toronto, ON, Canada. Electronic address: sachdev.sidhu@utoronto.ca.
Cell Rep ; 39(9): 110905, 2022 05 31.
Article in English | MEDLINE | ID: covidwho-1850802
ABSTRACT
Neutralizing antibodies (nAbs) that target the SARS-CoV-2 spike protein have received emergency use approval for treatment of COVID-19. However, with the emergence of variants of concern, there is a need for new treatment options. We report a format that enables modular assembly of bi-paratopic tetravalent nAbs with antigen-binding sites from two distinct nAbs. The tetravalent nAb purifies in high yield and exhibits biophysical characteristics that are comparable to those of clinically used therapeutic antibodies. The tetravalent nAb binds to the spike protein trimer at least 100-fold more tightly than bivalent IgGs (apparent KD < 1 pM) and neutralizes a broad array of SARS-CoV-2 pseudoviruses, chimeric viruses, and authentic viral variants with high potency. Together, these results establish the tetravalent diabody-Fc-Fab as a robust, modular platform for rapid production of drug-grade nAbs with potencies and breadth of coverage that greatly exceed those of conventional bivalent IgGs.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Prognostic study Topics: Variants Limits: Humans Language: English Journal: Cell Rep Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Prognostic study Topics: Variants Limits: Humans Language: English Journal: Cell Rep Year: 2022 Document Type: Article