Vanshylla, Kanika ORCID: 0000-0003-4552-9170, Fan, Chengcheng ORCID: 0000-0003-4213-5758, Wunsch, Marie ORCID: 0000-0002-6570-1831, Poopalasingam, Nareshkumar ORCID: 0000-0002-4981-6209, Meijers, Matthijs ORCID: 0000-0002-1876-8064, Kreer, Christoph ORCID: 0000-0002-9140-9850, Kleipass, Franziska ORCID: 0009-0003-7120-6620, Ruchnewitz, Denis ORCID: 0000-0001-5740-6958, Ercanoglu, Meryem S., Gruell, Henning, Muenn, Friederike, Pohl, Kai, Janicki, Hanna, Nolden, Tobias ORCID: 0000-0002-8996-5612, Bartl, Simone, Stein, Saskia C., Augustin, Max, Dewald, Felix, Gieselmann, Lutz, Schommers, Philipp, Schulz, Thomas F., Sander, Leif Erik, Koch, Manuel ORCID: 0000-0002-2962-7814, Luksza, Marta, Laessig, Michael, Bjorkman, Pamela J. and Klein, Florian ORCID: 0000-0003-1376-1792 (2022). Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers. Cell Host Microbe, 30 (1). S. 69 - 94. CAMBRIDGE: CELL PRESS. ISSN 1934-6069

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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 SARSCoV-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 upand downconformations 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Vanshylla, KanikaUNSPECIFIEDorcid.org/0000-0003-4552-9170UNSPECIFIED
Fan, ChengchengUNSPECIFIEDorcid.org/0000-0003-4213-5758UNSPECIFIED
Wunsch, MarieUNSPECIFIEDorcid.org/0000-0002-6570-1831UNSPECIFIED
Poopalasingam, NareshkumarUNSPECIFIEDorcid.org/0000-0002-4981-6209UNSPECIFIED
Meijers, MatthijsUNSPECIFIEDorcid.org/0000-0002-1876-8064UNSPECIFIED
Kreer, ChristophUNSPECIFIEDorcid.org/0000-0002-9140-9850UNSPECIFIED
Kleipass, FranziskaUNSPECIFIEDorcid.org/0009-0003-7120-6620UNSPECIFIED
Ruchnewitz, DenisUNSPECIFIEDorcid.org/0000-0001-5740-6958UNSPECIFIED
Ercanoglu, Meryem S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruell, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muenn, FriederikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pohl, KaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janicki, HannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nolden, TobiasUNSPECIFIEDorcid.org/0000-0002-8996-5612UNSPECIFIED
Bartl, SimoneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stein, Saskia C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Augustin, MaxUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dewald, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gieselmann, LutzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schommers, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulz, Thomas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sander, Leif ErikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koch, ManuelUNSPECIFIEDorcid.org/0000-0002-2962-7814UNSPECIFIED
Luksza, MartaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laessig, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bjorkman, Pamela J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDorcid.org/0000-0003-1376-1792UNSPECIFIED
URN: urn:nbn:de:hbz:38-690844
DOI: 10.1016/j.chom.2021.12.010
Journal or Publication Title: Cell Host Microbe
Volume: 30
Number: 1
Page Range: S. 69 - 94
Date: 2022
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1934-6069
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SINGLE-CELL; GENERATION; DOMAINMultiple languages
Microbiology; Parasitology; VirologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69084

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