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

Animals Antibodies, Monoclonal Antibodies, Viral COVID-19 Cryoelectron Microscopy Epitopes Haplorhini Humans Membrane Glycoproteins Neutralization Tests SARS-CoV-2 Spike Glycoprotein, Coronavirus Viral Envelope Proteins

Journal

Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869

Informations de publication

Date de publication:
09 2022
Historique:
received: 08 06 2022
accepted: 06 07 2022
pubmed: 26 7 2022
medline: 31 8 2022
entrez: 25 7 2022
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41564-022-01198-6 PMID: 35879526 PMC: PMC9418005
pubmed: 35879526
doi: 10.1038/s41564-022-01198-6
pii: 10.1038/s41564-022-01198-6
pmc: PMC9418005
doi:

Substances chimiques

Antibodies, Monoclonal 0
Antibodies, Viral 0
Epitopes 0
Membrane Glycoproteins 0
Spike Glycoprotein, Coronavirus 0
Viral Envelope Proteins 0
spike protein, SARS-CoV-2 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1376-1389

Informations de copyright

© 2022. The Author(s).

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Auteurs

Craig Fenwick (C)

Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
ORCID: 0000-0002-9435-0110

Priscilla Turelli (P)

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
ORCID: 0000-0002-7302-9977

Dongchun Ni (D)

School of Basic Sciences, Ecole Polytechnique Fédérale de Lausanne and Faculty of Biology and Medicine, UNIL, Lausanne, Switzerland.

Laurent Perez (L)

Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
ORCID: 0000-0002-8860-7928

Kelvin Lau (K)

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
ORCID: 0000-0002-9040-7597

Cécile Herate (C)

CEA, Université Paris Sud 11, INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, Fontenay-aux-Roses, France.

Romain Marlin (R)

CEA, Université Paris Sud 11, INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, Fontenay-aux-Roses, France.

Erica Lana (E)

Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Céline Pellaton (C)

Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Charlène Raclot (C)

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
ORCID: 0000-0002-1558-5916

Line Esteves-Leuenberger (L)

Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Jérémy Campos (J)

Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Alex Farina (A)

Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Flurin Fiscalini (F)

Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Nathalie Dereuddre-Bosquet (N)

CEA, Université Paris Sud 11, INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, Fontenay-aux-Roses, France.
ORCID: 0000-0001-6682-6313

Francis Relouzat (F)

CEA, Université Paris Sud 11, INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, Fontenay-aux-Roses, France.

Rana Abdelnabi (R)

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
ORCID: 0000-0001-9771-7312

Caroline S Foo (CS)

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
ORCID: 0000-0002-6380-4917

Johan Neyts (J)

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
ORCID: 0000-0002-0033-7514

Pieter Leyssen (P)

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
ORCID: 0000-0002-7537-1688

Yves Lévy (Y)

VRI, Université Paris-Est Créteil, Faculté de Médicine, INSERM U955, Créteil, France.
Inserm U955, Equipe 16, Créteil, France.
AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d'Immunologie Clinique et Maladies Infectieuses, Créteil, France.
ORCID: 0000-0002-5549-6256

Florence Pojer (F)

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Henning Stahlberg (H)

School of Basic Sciences, Ecole Polytechnique Fédérale de Lausanne and Faculty of Biology and Medicine, UNIL, Lausanne, Switzerland.
ORCID: 0000-0002-1185-4592

Roger LeGrand (R)

CEA, Université Paris Sud 11, INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, Fontenay-aux-Roses, France.

Didier Trono (D)

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. didier.trono@epfl.ch.
ORCID: 0000-0002-3383-0401

Giuseppe Pantaleo (G)

Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. giuseppe.pantaleo@chuv.ch.
Swiss Vaccine Research Institute, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. giuseppe.pantaleo@chuv.ch.
ORCID: 0000-0003-3651-2721

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Patient-derived monoclonal antibody...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Patient-derived monoclonal antibody...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps antiviraux › Patient-derived monoclonal antibody...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Patient-derived monoclonal antibody...
questionsmedicales.fr › Techniques d'investigation › Microscopie électronique › Cryomicroscopie électronique › Patient-derived monoclonal antibody...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Épitopes › Patient-derived monoclonal antibody...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Patient-derived monoclonal antibody...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Patient-derived monoclonal antibody...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Glycoprotéines membranaires › Patient-derived monoclonal antibody...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Tests immunologiques › Tests sérologiques › Tests de neutralisation › Patient-derived monoclonal antibody...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › Patient-derived monoclonal antibody...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales structurales › Protéines de l'enveloppe virale › Protéines de fusion virale › Glycoprotéine de spicule des coronavirus › Patient-derived monoclonal antibody...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales structurales › Protéines de l'enveloppe virale › Patient-derived monoclonal antibody...