The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies

• DOI: 10.1016/j.cell.2021.06.002
• Publication Date: 2021-06-05T17:17:42Z
• Authors: Richard Copin; Alina Baum; Elzbieta Wloga; Kristen E. Pascal; Stephanie Giordano; Benjamin O. Fulton; Anbo Zhou; Nicole Negron; Kathryn Lanza; Newton Chan; Angel Coppola; Joyce Chiu; Min Ni; Yi Wei; Gurinder S. Atwal; Annabel Romero He...; Kei Saotome; Yi Zhou; Matthew C. Franklin; Andrea T. Hooper; Shane McCarthy; Sara Hamon; Jennifer D. Hamilton; Hilary M. Staples; Kendra Alfson; Ricardo Carrion; Shazia Ali; Thomas Norton; Selin Somersan-Ka...; Sumathi Sivapalas...; Gary A. Herman; David M. Weinreich; Leah Lipsich; Neil Stahl; Andrew J. Murphy; George D. Yancopo...; Christos A. Kyrat...
• Keywords: Male; 0301 basic medicine; coronavirus; Article; lung; 03 medical and health sciences; Neutralization Tests; Cricetinae; organs types and functions; 616; Chlorocebus aethiops; Animals; Humans; genetics & nucleic acid processing; tissues; RNA structure; Lung; Vero Cells; antibody therapy; genomics and proteomics; function; modification; viral diseases; SARS-CoV-2; covid 19; Cryoelectron Microscopy; Antibodies, Monoclonal; COVID-19; bioinformatics; DNA; Viral Load; mutations; 3. Good health; Hospitalization; organelles; diseases & disorders; monoclonal antibody; Mutation; organs; cell types and functions

Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. Because rapidly emerging virus mutants are becoming the next major concern in the fight against the global pandemic, it is imperative that these therapeutic treatments provide coverage against circulating variants and do not contribute to development of treatment-induced emergent resistance. To this end, we investigated the sequence diversity of the spike protein and monitored emergence of virus variants in SARS-COV-2 isolates found in COVID-19 patients treated with the two-antibody combination REGEN-COV, as well as in preclinical in vitro studies using single, dual, or triple antibody combinations, and in hamster in vivo studies using REGEN-COV or single monoclonal antibody treatments. Our study demonstrates that the combination of non-competing antibodies in REGEN-COV provides protection against all current SARS-CoV-2 variants of concern/interest and also protects against emergence of new variants and their potential seeding into the population in a clinical setting.