tetano
Editor, Senior Moderator
Cell Host Microbe
. 2021 Dec 18;S1931-3128(21)00581-3.
doi: 10.1016/j.chom.2021.12.010. Online ahead of print.
Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers
Kanika Vanshylla[SUP] 1 [/SUP], Chengcheng Fan[SUP] 2 [/SUP], Marie Wunsch[SUP] 1 [/SUP], Nareshkumar Poopalasingam[SUP] 1 [/SUP], Matthijs Meijers[SUP] 3 [/SUP], Christoph Kreer[SUP] 1 [/SUP], Franziska Kleipass[SUP] 1 [/SUP], Denis Ruchnewitz[SUP] 3 [/SUP], Meryem S Ercanoglu[SUP] 1 [/SUP], Henning Gruell[SUP] 1 [/SUP], Friederike Münn[SUP] 4 [/SUP], Kai Pohl[SUP] 4 [/SUP], Hanna Janicki[SUP] 1 [/SUP], Tobias Nolden[SUP] 5 [/SUP], Simone Bartl[SUP] 6 [/SUP], Saskia C Stein[SUP] 7 [/SUP], Max Augustin[SUP] 8 [/SUP], Felix Dewald[SUP] 1 [/SUP], Lutz Gieselmann[SUP] 1 [/SUP], Philipp Schommers[SUP] 9 [/SUP], Thomas F Schulz[SUP] 7 [/SUP], Leif Erik Sander[SUP] 4 [/SUP], Manuel Koch[SUP] 10 [/SUP], Marta Łuksza[SUP] 11 [/SUP], Michael Lässig[SUP] 3 [/SUP], Pamela J Bjorkman[SUP] 2 [/SUP], Florian Klein[SUP] 12 [/SUP]
Affiliations
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.
. 2021 Dec 18;S1931-3128(21)00581-3.
doi: 10.1016/j.chom.2021.12.010. Online ahead of print.
Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers
Kanika Vanshylla[SUP] 1 [/SUP], Chengcheng Fan[SUP] 2 [/SUP], Marie Wunsch[SUP] 1 [/SUP], Nareshkumar Poopalasingam[SUP] 1 [/SUP], Matthijs Meijers[SUP] 3 [/SUP], Christoph Kreer[SUP] 1 [/SUP], Franziska Kleipass[SUP] 1 [/SUP], Denis Ruchnewitz[SUP] 3 [/SUP], Meryem S Ercanoglu[SUP] 1 [/SUP], Henning Gruell[SUP] 1 [/SUP], Friederike Münn[SUP] 4 [/SUP], Kai Pohl[SUP] 4 [/SUP], Hanna Janicki[SUP] 1 [/SUP], Tobias Nolden[SUP] 5 [/SUP], Simone Bartl[SUP] 6 [/SUP], Saskia C Stein[SUP] 7 [/SUP], Max Augustin[SUP] 8 [/SUP], Felix Dewald[SUP] 1 [/SUP], Lutz Gieselmann[SUP] 1 [/SUP], Philipp Schommers[SUP] 9 [/SUP], Thomas F Schulz[SUP] 7 [/SUP], Leif Erik Sander[SUP] 4 [/SUP], Manuel Koch[SUP] 10 [/SUP], Marta Łuksza[SUP] 11 [/SUP], Michael Lässig[SUP] 3 [/SUP], Pamela J Bjorkman[SUP] 2 [/SUP], Florian Klein[SUP] 12 [/SUP]
Affiliations
- PMID: 34973165
- DOI: 10.1016/j.chom.2021.12.010
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.