Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers
| Autor: | Kanika Vanshylla, Chengcheng Fan, Marie Wunsch, Nareshkumar Poopalasingam, Matthijs Meijers, Christoph Kreer, Franziska Kleipass, Denis Ruchnewitz, Meryem S. Ercanoglu, Henning Gruell, Friederike Münn, Kai Pohl, Hanna Janicki, Tobias Nolden, Simone Bartl, Saskia C. Stein, Max Augustin, Felix Dewald, Lutz Gieselmann, Philipp Schommers, Thomas F. Schulz, Leif Erik Sander, Manuel Koch, Marta Łuksza, Michael Lässig, Pamela J. Bjorkman, Florian Klein |
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| Jazyk: | angličtina |
| Předmět: |
Male
SARS-CoV-2 Antibodies Monoclonal COVID-19 Cross Reactions Middle Aged Antibodies Viral Microbiology Article HEK293 Cells Neutralization Tests Virology Chlorocebus aethiops Spike Glycoprotein Coronavirus Animals Humans Female Parasitology Vero Cells Broadly Neutralizing Antibodies Cells Cultured |
| Zdroj: | Cell Host & Microbe Cell Host Microbe |
| ISSN: | 1931-3128 |
| DOI: | 10.1016/j.chom.2021.12.010 |
| Popis: | 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, B1.351, B.1.429, B.1.617, 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. Graphical Abstract Vanshylla et al. deciphered the antibody response in SARS-CoV-2 convalescent elite neutralizers on a single B-cell level. Isolated antibodies were highly potent and neutralized various mutants including the predominant variants of concern and emerging variants. Structural analysis of one ultrapotent IGHV3-53/IGKV1-9 bNAb revealed a flexible binding mechanism to the RBD. |
| Databáze: | OpenAIRE |
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