As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health worldwide, the development of effective interventions is urgently needed. Neutralizing antibodies (nAbs) have great potential for the prevention and treatment of SARS-CoV-2 infection. In this study, ten nAbs were isolated from two phage-display immune libraries constructed from the pooled PBMCs of eight COVID-19 convalescent patients. Eight of them, consisting of heavy chains encoded by the immunoglobulin heavy-chain gene-variable region ( IGHV )3-66 or IGHV 3-53 genes, recognized the same epitope on the receptor-binding domain (RBD), while the remaining two bound to different epitopes. Among the ten antibodies, 2B11 exhibited the highest affinity and neutralization potency against the original wild-type (WT) SARS-CoV-2 virus (K D = 4.76 nM for the S1 protein, IC 50 = 6 ng/mL for pseudoviruses, and IC 50 = 1 ng/mL for authentic viruses), and potent neutralizing ability against B.1.1.7 pseudoviruses. Furthermore, 1E10, targeting a distinct epitope on RBD, exhibited different neutralization efficiency against WT SARS-CoV-2 and its variants B.1.1.7, B.1.351, and P.1. The crystal structure of the 2B11–RBD complexes revealed that the epitope of 2B11 highly overlaps with the ACE2-binding site. The in vivo experiment of 2B11 using AdV5-hACE2-transduced mice showed encouraging therapeutic and prophylactic efficacy against SARS-CoV-2. Taken together, our results suggest that the highly potent SARS-CoV-2-neutralizing antibody, 2B11, could be used against the WT SARS-CoV-2 and B.1.1.7 variant, or in combination with a different epitope-targeted neutralizing antibody, such as 1E10, against SARS-CoV-2 variants.
【저자키워드】 immunology, structural biology, 【초록키워드】 Treatment, viruses, neutralizing antibody, public health, antibodies, SARS-CoV-2, Efficacy, coronavirus, antibody, B.1.351, neutralization, SARS-COV-2 infection, variant, SARS-CoV-2 virus, Prophylactic, immune, Epitopes, B.1.1.7 variant, Immunoglobulin, SARS-CoV-2 variants, B.1.1.7, mice, RBD, P.1, therapeutic, PBMC, Neutralizing, experiment, in vivo, epitope, NAb, Combination, Efficiency, pseudoviruses, heavy chain, acute respiratory syndrome, overlap, effective intervention, neutralization potency, wild-type, highest affinity, WT SARS-CoV-2, Genes, COVID-19 convalescent patients, eight, exhibited, the receptor-binding domain, complexes, the S1 protein, 2B11, ACE2-binding site, IGHV, SARS-CoV-2-neutralizing antibody, 【제목키워드】 neutralizing antibody, SARS-CoV-2, Screening, convalescent,