[PDF][PDF] Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers

K Vanshylla, C Fan, M Wunsch, N Poopalasingam… - Cell host & …, 2022 - cell.com
K Vanshylla, C Fan, M Wunsch, N Poopalasingam, M Meijers, C Kreer, F Kleipass…
Cell host & microbe, 2022cell.com
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 …
Summary
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.
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