Human Monoclonal Antibodies Against SARS-CoV-2

Two human monoclonal antibodies that potently neutralize Chikungunya virus both in vitro and in vivo.

Most monoclonal antibody therapies have consisted of single monoclonal antibodies. In this study, we describe four human monoclonal antibodies designed to function as a cocktail, each targeting distinct regions of the virus. By binding from different angles, this approach has the potential to be effective against a much broader range of variants.

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in roughly 466 million cases and 6 million deaths worldwide. Intense global efforts were pursued to develop, evaluate and implement vaccines or other interventions such as human monoclonal antibody (mAb) therapy. Widespread transmission and key mutations further led to the regular emergence of viral variants that escape neutralization to therapeutic antibodies as well as natural and vaccine acquired immunity. Therefore, it was established that there was a need for therapeutics that have a broad spectrum of action across most variants of concern/interest (VOCs / VOIs). We generated 93 human monoclonal antibodies against SARS-CoV-2, of which we solved structures for 4 antibodies that potently neutralized many of the earlier variants of SARS-CoV-2, along with one antibody that maintained its potency multiple variants including Omicron lineages.

Any individual that has SARS-CoV-2 infection and is not responding to the standard clinical regime

All four human monoclonal antibodies bind to different regions of the SARS-CoV-2 receptor binding domain and thus neutralize the virus. The F2 human monoclonal that is most broadly neutralizing does not bind to the ACE2-RBD axis but in a very conserved region of RBD that does not allow RBD trimer to open up and interact with Ace2.

Mab F2 was described in: Structural insights for neutralization of Omicron
variants BA.1, BA.2, BA.4, and BA.5 by a broadly neutralizing SARS-CoV-2 antibody. Science advances, 5th Oct 2022.
The other three mabs (002-02, 002-13, 034-32 were described in: Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response. Structure, 6th July 2023.