Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers

Edurne Rujas, Iga Kucharska, Yong Zi Tan, Samir Benlekbir, Hong Cui, Tiantian Zhao, Gregory A. Wasney, Patrick Budylowski, Furkan Guvenc, Jocelyn C. Newton, Taylor Sicard, Anthony Semesi, Krithika Muthuraman, Amy Nouanesengsy, Clare Burn Aschner, Katherine Prieto, Stephanie A. Bueler, Sawsan Youssef, Sindy Liao-Chan, Jacob Glanville, Natasha Christie-Holmes, Samira Mubareka, Scott D. Gray-Owen, John L. Rubinstein, Bebhinn Treanor and Jean-Philippe Julien ()
Additional contact information
Edurne Rujas: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Iga Kucharska: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Yong Zi Tan: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Samir Benlekbir: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Hong Cui: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Tiantian Zhao: University of Toronto
Gregory A. Wasney: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Patrick Budylowski: University of Toronto
Furkan Guvenc: University of Toronto
Jocelyn C. Newton: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Taylor Sicard: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Anthony Semesi: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Krithika Muthuraman: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Amy Nouanesengsy: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Clare Burn Aschner: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Katherine Prieto: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Stephanie A. Bueler: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Sawsan Youssef: Distributed Bio
Sindy Liao-Chan: Distributed Bio
Jacob Glanville: Distributed Bio
Natasha Christie-Holmes: University of Toronto
Samira Mubareka: University of Toronto
Scott D. Gray-Owen: University of Toronto
John L. Rubinstein: Program in Molecular Medicine, The Hospital for Sick Children Research Institute
Bebhinn Treanor: University of Toronto
Jean-Philippe Julien: Program in Molecular Medicine, The Hospital for Sick Children Research Institute

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-23825-2

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