Abstract
As the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants of concern (VoCs). Here, we evaluate the potency of a previously described mAb J08 against these variants using cell-based assays and delve into the molecular details of the binding interaction using cryo-EM. We show that mAb J08 has low nanomolar affinity against VoCs, binds high on the receptor binding domain (RBD) ridge and is therefore unaffected by most mutations, and can bind in the RBD-up and -down conformations. These findings further validate the phase II/III human clinical trial underway using mAb J08 as a monoclonal therapy.
One Sentence Summary Potent neutralizing monoclonal antibody J08 binds SARS-CoV-2 spike independent of known escape mutations.
Competing Interest Statement
Rino Rappuoli is an employee of GSK group of companies. E.A., I.P., N.M., E.P., P.P., C.S. and R.R. are listed as inventors of full-length human monoclonal antibodies described in Italian patent applications n. 102020000015754 filed on June 30, 2020, 102020000018955 filed on August 3, 2020 and 102020000029969 filed on December 4, 2020, and the international patent system number PCT/IB2021/055755 filed on June 28, 2021. The other authors declare that they have no competing interests.
Footnotes
This version of the manuscript corrects an author name and includes minor formatting edits.