Potent monoclonal antibodies neutralize Omicron sublineages and other SARS-CoV-2 variants

The emergence and global spread of the SARS-CoV-2 Omicron variants, which carry an unprecedented number of mutations, raise serious concerns due to the reduced efficacy of current vaccines and resistance to therapeutic antibodies. Here, we report the generation and characterization of two potent human monoclonal antibodies, NA8 and NE12, against the receptor-binding domain of the SARS-CoV-2 spike protein. NA8 interacts with a highly conserved region and has a breadth of neutralization with picomolar potency against the Beta variant and the Omicron BA.1 and BA.2 sublineages and nanomolar potency against BA.2.12.1 and BA.4. Combination of NA8 and NE12 retains potent neutralizing activity against the major SARS-CoV-2 variants of concern. Cryo-EM analysis provides the structural basis for the broad and complementary neutralizing activity of these two antibodies. We confirm the in vivo protective and therapeutic efficacies of NA8 and NE12 in the hamster model. These results show that broad and potent human antibodies can overcome the continuous immune escape of evolving SARS-CoV-2 variants. [Display omitted] •Monoclonal antibodies are isolated from COVID-19 convalescent patients•NA8 and NE12 potently neutralize newly emerging SARS-CoV-2 variants of concern•Structural analysis reveals a unique conserved binding epitope for NA8•NA8 and NE12 show prophylactic and therapeutic efficacy in the Syrian hamster model The emergence of new SARS-CoV-2 variants that escape neutralization can jeopardize the efficacy of vaccines and therapeutic antibodies. Chen et al. report the isolation of potent human antibodies that neutralize emerging variants of concern, including various Omicron sublineages. These antibodies show prophylactic and therapeutic efficacy in the hamster model.