Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34135340.
- Also identified by DOI 10.1038/s41467-021-23825-2 and PMC identifier 8209050.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (IC<sub>50</sub>) values as low as 9 × 10<sup>-</sup><sup>14</sup> 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.
Medical subject headings
- Antibodies, Monoclonal
- Antibodies, Neutralizing
- Antibodies, Viral
- SARS-CoV-2