Extremely potent human monoclonal antibodies from COVID-19 convalescent patients

Human monoclonal antibodies are safe, preventive, and therapeutic tools that can be rapidly developed to help restore the massive health and economic disruption caused by the coronavirus disease 2019 (COVID-19) pandemic. By single-cell sorting 4,277 SARS-CoV-2 spike protein-specific memory B cells from 14 COVID-19 survivors, 453 neutralizing antibodies were identified. The most potent neutralizing antibodies recognized the spike protein receptor-binding domain, followed in potency by antibodies that recognize the S1 domain, the spike protein trimer, and the S2 subunit. Only 1.4% of them neutralized the authentic virus with a potency of 1-10 ng/mL. The most potent monoclonal antibody, engineered to reduce the risk of antibody-dependent enhancement and prolong half-life, neutralized the authentic wild-type virus and emerging variants containing D614G, E484K, and N501Y substitutions. Prophylactic and therapeutic efficacy in the hamster model was observed at 0.25 and 4 mg/kg respectively in absence of Fc functions.

Automated summary

Human monoclonal antibodies have been identified as safe, preventive, and therapeutic tools against COVID-19. Through single-cell sorting from COVID-19 survivors, a large number of spike protein-specific memory B cells have been identified, leading to the discovery of highly effective neutralizing antibodies. The most potent monoclonal antibody, engineered to reduce risk and prolong half-life, has been shown to neutralize both the original virus and emerging variants.