Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus with a high mutation rate. Importantly, several currently circulating SARS-CoV-2 variants are associated with loss of efficacy for both vaccines and neutralizing antibodies. Methods We analyzed the binding activity of six highly potent antibodies to the spike proteins of SARS-CoV-2 variants, assessed their neutralizing abilities with pseudovirus and authentic SARS-CoV-2 variants and evaluate efficacy of antibody cocktail in Delta SARS-CoV-2-infected hamster models as prophylactic and post-infection treatments. Results The tested RBD-chAbs, except RBD-chAb-25, maintained binding ability to spike proteins from SARS-CoV-2 variants. However, only RBD-chAb-45 and -51 retained neutralizing activities; RBD-chAb-1, -15, -25 and -28 exhibited diminished neutralization for all SARS-CoV-2 variants. Notably, several cocktails of our antibodies showed low IC 50 values (3.35–27.06 ng/ml) against the SARS-CoV-2 variant pseudoviruses including United Kingdom variant B.1.1.7 (Alpha), South Africa variant B.1.351 (Beta), Brazil variant P1 (Gamma), California variant B.1.429 (Epsilon), New York variant B.1.526 (Iota), and India variants, B.1.617.1 (Kappa) and B.1.617.2 (Delta). RBD-chAb-45, and -51 showed PRNT 50 values 4.93–37.54 ng/ml when used as single treatments or in combination with RBD-chAb-15 or -28, according to plaque assays with authentic Alpha, Gamma and Delta SARS-CoV-2 variants. Furthermore, the antibody cocktail of RBD-chAb-15 and -45 exhibited potent prophylactic and therapeutic effects in Delta SARS-CoV-2 variant-infected hamsters. Conclusions The cocktail of RBD-chAbs exhibited potent neutralizing activities against SARS-CoV-2 variants. These antibody cocktails are highly promising candidate tools for controlling new SARS-CoV-2 variants, including Delta.
【저자키워드】 neutralizing antibody, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Receptor-binding domain (RBD), Cocktail therapy, 【초록키워드】 COVID-19, Treatment, coronavirus disease, Brazil, SARS-CoV-2, Coronavirus disease 2019, Efficacy, Vaccine, coronavirus, Neutralizing antibodies, antibody, hamsters, B.1.351, neutralization, India, variant, SARS-CoV-2 variant, Delta, B.1.617.2, Prophylactic, severe acute respiratory syndrome Coronavirus, variants, Spike protein, Neutralizing activity, South Africa, antibody cocktail, SARS-CoV-2 variants, pseudovirus, B.1.1.7, Epsilon, B.1.617.1, Gamma, Alpha, B.1.429, Beta, Neutralizing, B.1.526, RNA virus, respiratory, United Kingdom, New York, mutation rate, PRNT, cocktail, Combination, Plaque assay, Spike proteins, Iota, binding activity, pseudoviruses, (Beta), (Alpha), Post-infection, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, therapeutic effect, high mutation rate, neutralizing activities, plaque assays, binding ability, new SARS-CoV-2, Result, tested, analyzed, evaluate, caused, exhibited, the spike protein, retained, circulating SARS-CoV-2 variant, the SARS-CoV-2, 【제목키워드】 variants of SARS-CoV-2, effective,