Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 in patients receiving monoclonal antibodies

Timothée Bruel; Karl Stéfic; Yann Nguyen; Donatella Toniutti; Isabelle Staropoli; Françoise Porrot; Florence Guivel-Benhassine; William-Henry Bolland; Delphine Planas; Jérôme Hadjadj; Lynda Handala; Cyril Planchais; Matthieu Prot; Etienne Simon-Lorière; Emmanuel André; Guy Baele; Lize Cuypers; Luc Mouthon; Hugo Mouquet; Julian Buchrieser; Aymeric Sève; Thierry Prazuck; Piet Maes; Benjamin Terrier; Laurent Hocqueloux; Olivier Schwartz

doi:10.1016/j.xcrm.2022.100850

Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 in patients receiving monoclonal antibodies

Cell Rep Med. 2022 Dec 20;3(12):100850. doi: 10.1016/j.xcrm.2022.100850. Epub 2022 Nov 17.

Authors

Timothée Bruel¹, Karl Stéfic², Yann Nguyen³, Donatella Toniutti⁴, Isabelle Staropoli⁴, Françoise Porrot⁴, Florence Guivel-Benhassine⁴, William-Henry Bolland⁵, Delphine Planas⁶, Jérôme Hadjadj³, Lynda Handala², Cyril Planchais⁷, Matthieu Prot⁸, Etienne Simon-Lorière⁸, Emmanuel André⁹, Guy Baele¹⁰, Lize Cuypers¹¹, Luc Mouthon³, Hugo Mouquet⁷, Julian Buchrieser⁴, Aymeric Sève¹², Thierry Prazuck¹², Piet Maes¹⁰, Benjamin Terrier³, Laurent Hocqueloux¹², Olivier Schwartz¹³

Affiliations

¹ Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France; Vaccine Research Institute, Créteil, France. Electronic address: timothee.bruel@pasteur.fr.
² INSERM U1259, Université de Tours, Tours, France; CHRU de Tours, National Reference Center for HIV-Associated Laboratory, Tours, France.
³ Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP.CUP, Hopital Cochin, Paris, France.
⁴ Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France.
⁵ Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France; Université Paris Cité, École doctorale BioSPC 562, Paris, France.
⁶ Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France; Vaccine Research Institute, Créteil, France.
⁷ Humoral Immunology Laboratory, Institut Pasteur, Université Paris Cité, INSERM U1222, Paris, France.
⁸ G5 Evolutionary Genomics of RNA Viruses, Institut Pasteur, Université Paris Cité, Paris, France.
⁹ University Hospitals Leuven, Department of Laboratory Medicine, National Reference Centre for Respiratory Pathogens, Leuven, Belgium; KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical Microbiology, Leuven, Belgium.
¹⁰ KU Leuven, Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Leuven, Belgium.
¹¹ University Hospitals Leuven, Department of Laboratory Medicine, National Reference Centre for Respiratory Pathogens, Leuven, Belgium.
¹² CHR d'Orléans, Service de Maladies Infectieuses, Orléans, France.
¹³ Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France; Vaccine Research Institute, Créteil, France. Electronic address: olivier.schwatrtz@pasteur.fr.

Abstract

The emergence of Omicron sublineages impacts the therapeutic efficacy of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs). Here, we evaluate neutralization and antibody-dependent cellular cytotoxicity (ADCC) activities of 6 therapeutic mAbs against Delta, BA.2, BA.4, and BA.5. The Omicron subvariants escape most antibodies but remain sensitive to bebtelovimab and cilgavimab. Consistent with their shared spike sequence, BA.4 and BA.5 display identical neutralization profiles. Sotrovimab is the most efficient at eliciting ADCC. We also analyze 121 sera from 40 immunocompromised individuals up to 6 months after infusion of Ronapreve (imdevimab + casirivimab) or Evusheld (cilgavimab + tixagevimab). Sera from Ronapreve-treated individuals do not neutralize Omicron subvariants. Evusheld-treated individuals neutralize BA.2 and BA.5, but titers are reduced. A longitudinal evaluation of sera from Evusheld-treated patients reveals a slow decay of mAb levels and neutralization, which is faster against BA.5. Our data shed light on antiviral activities of therapeutic mAbs and the duration of effectiveness of Evusheld pre-exposure prophylaxis.

Keywords: ADCC; Omicron; SARS-CoV-2; antibodies; neutralization.

Publication types

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

MeSH terms

Antibodies, Monoclonal / therapeutic use
Antibody-Dependent Cell Cytotoxicity
Antiviral Agents / therapeutic use
COVID-19*
Humans
SARS-CoV-2*

Substances

Antibodies, Monoclonal
Antiviral Agents