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Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers.
Rujas, Edurne; Kucharska, Iga; Tan, Yong Zi; Benlekbir, Samir; Cui, Hong; Zhao, Tiantian; Wasney, Gregory A; Budylowski, Patrick; Guvenc, Furkan; Newton, Jocelyn C; Sicard, Taylor; Semesi, Anthony; Muthuraman, Krithika; Nouanesengsy, Amy; Aschner, Clare Burn; Prieto, Katherine; Bueler, Stephanie A; Youssef, Sawsan; Liao-Chan, Sindy; Glanville, Jacob; Christie-Holmes, Natasha; Mubareka, Samira; Gray-Owen, Scott D; Rubinstein, John L; Treanor, Bebhinn; Julien, Jean-Philippe.
  • Rujas E; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Kucharska I; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
  • Tan YZ; Biofisika Institute (CSIC, UPV/EHU) and Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), Bilbao, Spain.
  • Benlekbir S; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Cui H; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Zhao T; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Wasney GA; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Budylowski P; Department of Immunology, University of Toronto, Toronto, ON, Canada.
  • Guvenc F; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Newton JC; The Structural & Biophysical Core Facility, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Sicard T; Combined Containment Level 3 Unit, University of Toronto, Toronto, ON, Canada.
  • Semesi A; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
  • Muthuraman K; Combined Containment Level 3 Unit, University of Toronto, Toronto, ON, Canada.
  • Nouanesengsy A; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
  • Aschner CB; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Prieto K; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Bueler SA; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
  • Youssef S; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Liao-Chan S; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Glanville J; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Christie-Holmes N; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
  • Mubareka S; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Gray-Owen SD; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Rubinstein JL; Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
  • Treanor B; Distributed Bio, South San Francisco, CA, USA.
  • Julien JP; Distributed Bio, South San Francisco, CA, USA.
Nat Commun ; 12(1): 3661, 2021 06 16.
Article in English | MEDLINE | ID: covidwho-1275912
ABSTRACT
SARS-CoV-2, the virus responsible for COVID-19, has caused a global pandemic. Antibodies can be powerful biotherapeutics to fight viral infections. Here, we use the human apoferritin protomer as a modular subunit to drive oligomerization of antibody fragments and transform antibodies targeting SARS-CoV-2 into exceptionally potent neutralizers. Using this platform, half-maximal inhibitory concentration (IC50) values as low as 9 × 10-14 M are achieved as a result of up to 10,000-fold potency enhancements compared to corresponding IgGs. Combination of three different antibody specificities and the fragment crystallizable (Fc) domain on a single multivalent molecule conferred the ability to overcome viral sequence variability together with outstanding potency and IgG-like bioavailability. The MULTi-specific, multi-Affinity antiBODY (Multabody or MB) platform thus uniquely leverages binding avidity together with multi-specificity to deliver ultrapotent and broad neutralizers against SARS-CoV-2. The modularity of the platform also makes it relevant for rapid evaluation against other infectious diseases of global health importance. Neutralizing antibodies are a promising therapeutic for SARS-CoV-2.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / SARS-CoV-2 / Antibodies, Monoclonal / Antibodies, Viral Type of study: Experimental Studies Limits: Animals / Humans / Male Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-23825-2

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / SARS-CoV-2 / Antibodies, Monoclonal / Antibodies, Viral Type of study: Experimental Studies Limits: Animals / Humans / Male Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-23825-2