Patient-derived monoclonal antibody neutralizes SARS-CoV-2 Omicron variants and confers full protection in monkeys.

Details

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_539E1A543541
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Patient-derived monoclonal antibody neutralizes SARS-CoV-2 Omicron variants and confers full protection in monkeys.
Journal
Nature microbiology
Author(s)
Fenwick C. (co-first), Turelli P. (co-first), Ni D. (co-first), Perez L. (co-first), Lau K., Herate C., Marlin R., Lana E., Pellaton C., Raclot C., Esteves-Leuenberger L., Campos J., Farina A., Fiscalini F., Dereuddre-Bosquet N., Relouzat F., Abdelnabi R., Foo C.S., Neyts J., Leyssen P., Lévy Y., Pojer F., Stahlberg H., LeGrand R., Trono D., Pantaleo G.
ISSN
2058-5276 (Electronic)
ISSN-L
2058-5276
Publication state
Published
Issued date
25/07/2022
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
The SARS-CoV-2 Omicron variant has very high levels of transmission, is resistant to neutralization by authorized therapeutic human monoclonal antibodies (mAb) and is less sensitive to vaccine-mediated immunity. To provide additional therapies against Omicron, we isolated a mAb named P2G3 from a previously infected vaccinated donor and showed that it has picomolar-range neutralizing activity against Omicron BA.1, BA.1.1, BA.2 and all other variants tested. We solved the structure of P2G3 Fab in complex with the Omicron spike using cryo-electron microscopy at 3.04 Å resolution to identify the P2G3 epitope as a Class 3 mAb that is different from mAb-binding spike epitopes reported previously. Using a SARS-CoV-2 Omicron monkey challenge model, we show that P2G3 alone, or in combination with P5C3 (a broadly active Class 1 mAb previously identified), confers complete prophylactic or therapeutic protection. Although we could select for SARS-CoV-2 mutants escaping neutralization by P2G3 or by P5C3 in vitro, they had low infectivity and 'escape' mutations are extremely rare in public sequence databases. We conclude that this combination of mAbs has potential as an anti-Omicron drug.
Keywords
Cell Biology, Microbiology (medical), Genetics, Applied Microbiology and Biotechnology, Immunology, Microbiology
Pubmed
Web of science
Open Access
Yes
Create date
27/07/2022 8:44
Last modification date
15/09/2022 5:38
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