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

Cell Host Microbe. 2021 Dec 18:S1931-3128(21)00581-3. doi: 10.1016/j.chom.2021.12.010. Online ahead of print.ABSTRACTA 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.PMID:34973165 | DOI:10.1016/j.chom.2021.12.010

Source: Cell Host and Microbe - January 1, 2022 Category: Microbiology Authors: Kanika Vanshylla Chengcheng Fan Marie Wunsch Nareshkumar Poopalasingam Matthijs Meijers Christoph Kreer Franziska Kleipass Denis Ruchnewitz Meryem S Ercanoglu Henning Gruell Friederike M ünn Kai Pohl Hanna Janicki Tobias Nolden Simone Bartl Saskia C Stei Source Type: research