Abstract
A fraction of COVID-19 convalescent individuals mount a potent antibody response to SARS-CoV-2 with cross-reactivity to SARS-CoV-1. To uncover their humoral response in detail, we performed single B cell analysis from 10 SARS-CoV-2 elite neutralizers. We isolated and analyzed 126 monoclonal antibodies, many of which were sarbecovirus cross-reactive, with some displaying merbecovirus- and embecovirus-reactivity. Several isolated broadly neutralizing antibodies were effective against B.1.1.7, B.1.351, B.1.429, B.1.617, and B.1.617.2 variants and 19 prominent potential escape sites. Furthermore, assembly of 716,806 SARS-CoV-2 sequences predicted emerging escape variants, which were also effectively neutralized. One of these broadly neutralizing potent antibodies, R40-1G8, is a IGHV3-53 RBD-class-1 antibody. Remarkably, cryo-EM analysis revealed that R40-1G8 has a flexible binding mode, targeting both “up” and “down” conformations of the RBD. Given the threat of emerging SARS-CoV-2 variants, we demonstrate that elite neutralizers are a valuable source for isolating ultrapotent antibody candidates to prevent and treat SARS-CoV-2 infection.
Keywords: COVID-19; SARS-CoV-2; broadly neutralizing antibodies; cryo-EM; emerging variants; ultrapotent monoclonal antibodies; variants of concern.
【저자키워드】 COVID-19, SARS-CoV-2, emerging variants, cryo-EM, broadly neutralizing antibodies, variants of concern., ultrapotent monoclonal antibodies, 【초록키워드】 neutralizing antibody, antibodies, Neutralizing antibodies, antibody, B.1.351, SARS-COV-2 infection, Antibody Response, variant, variants of concern, B.1.617.2, monoclonal antibodies, SARS-CoV-1, variants, cross-reactivity, SARS-CoV-2 variants, B.1.1.7, B.1.617, B.1.429, Neutralizing, cryo-EM, IGHV3-53, monoclonal, assembly, binding, sarbecovirus, Analysis, humoral, cross-reactive, conformation, SARS-CoV-2 sequence, candidate, treat, fraction, convalescent individuals, cryo, Prevent, effective, neutralized, Cryo-EM analysis, flexible, convalescent individual, predicted, analyzed, performed, the RBD, displaying, single B cell, 【제목키워드】 neutralizing antibody,