ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic resulting in millions of deaths worldwide. Despite the development and deployment of highly effective antibody and vaccine countermeasures, rapidly-spreading SARS-CoV-2 variants with mutations at key antigenic sites in the spike protein jeopardize their efficacy. Indeed, the recent emergence of the highly-transmissible B.1.1.529 Omicron variant is especially concerning because of the number of mutations, deletions, and insertions in the spike protein. Here, using a panel of anti-receptor binding domain (RBD) monoclonal antibodies (mAbs) corresponding to those with emergency use authorization (EUA) or in advanced clinical development by Vir Biotechnology (S309, the parent mAbs of VIR-7381), AstraZeneca (COV2-2196 and COV2-2130, the parent mAbs of AZD8895 and AZD1061), Regeneron (REGN10933 and REGN10987), Lilly (LY-CoV555 and LY-CoV016), and Celltrion (CT-P59), we report the impact on neutralization of a prevailing, infectious B.1.1.529 Omicron isolate compared to a historical WA1/2020 D614G strain. Several highly neutralizing mAbs (LY-CoV555, LY-CoV016, REGN10933, REGN10987, and CT-P59) completely lost inhibitory activity against B.1.1.529 virus in both Vero-TMPRSS2 and Vero-hACE2-TMPRSS2 cells, whereas others were reduced (∼12-fold decrease, COV2-2196 and COV2-2130 combination) or minimally affected (S309). Our results suggest that several, but not all, of the antibody products in clinical use will lose efficacy against the B.1.1.529 Omicron variant and related strains.
Competing Interest Statement
M.S.D. is a consultant for Inbios, Vir Biotechnology, Senda Bioscences, and Carnival Corporation, and on the Scientific Advisory Boards of Moderna and Immune. The Diamond laboratory has received funding from Moderna, Vir Biotechnology, and Emergent BioSolutions. J.E.C. has served as a consultant for Luna Biologics and Merck Sharp and Dohme Corp., is a member of the Scientific Advisory Boards of Meissa Vaccines, and is Founder of IDBiologics. The Crowe laboratory has received sponsored research agreements from Takeda Vaccines, AstraZeneca and IDBiologics. Vanderbilt University has applied for patents related to two antibodies in this paper. L.A.P. and D.C. are employees of Vir Biotechnology and may hold equity in Vir Biotechnology. L.A.P is a former employee and shareholder in Regeneron Pharmaceuticals.
