Multivalency Transforms SARS-CoV-2 Antibodies Into Ultrapotent Neutralizers
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Date
2021-06-16Author
Rujas Díez, 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
Burn Aschner, Clare
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
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Nature Communications 12(1) : (2021) // Article ID 3661
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, multiAffinity antiBODY (Multabody or MB) platform thus uniquely leverages binding avidity
together with multi-specificity to deliver ultrapotent and broad neutralizers against SARSCoV-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.