Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP.3.3 From Approved Monoclonal Antibodies

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Published: Sep 30, 2024
DOI: https://doi.org/10.20411/pai.v10i1.752

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Delphine Planas
Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris; Vaccine Research Institute, Créteil, France
Isabelle Staropoli
Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France
Cyril Planchais
Humoral Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France
Emilie Yab
National Reference Center for Respiratory Viruses, Molecular Mechanisms of Multiplication of Pneumoviruses Unit, Institut Pasteur, Université Paris Cité, Paris, France
Banujaa Jeyarajah
National Reference Center for Respiratory Viruses, Molecular Mechanisms of Multiplication of Pneumoviruses Unit, Institut Pasteur, Université Paris Cité, Paris, France
Yannis Rahou
National Reference Center for Respiratory Viruses, Molecular Mechanisms of Multiplication of Pneumoviruses Unit, Institut Pasteur, Université Paris Cité, Paris, France
Matthieu Prot
G5 Evolutionary Genomics of RNA Viruses, Institut Pasteur, Université Paris Cité, Paris, France
Florence Guivel-Benhassine
Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France
Frederic Lemoine
Bioinformatics and Biostatistics Hub, Paris, France
Vincent Enouf
National Reference Center for Respiratory Viruses, Molecular Mechanisms of Multiplication of Pneumoviruses Unit, Institut Pasteur, Université Paris Cité, Paris, France
Etienne Simon-Loriere
G5 Evolutionary Genomics of RNA Viruses, Institut Pasteur, Université Paris Cité, Paris, France
Hugo Mouquet
Humoral Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France
Marie-Anne Rameix-Welti
National Reference Center for Respiratory Viruses, Molecular Mechanisms of Multiplication of Pneumoviruses Unit, Institut Pasteur, Université Paris Cité; Molecular Mechanisms of Multiplication of Pneumoviruses, Université Paris-Saclay, Université de Versailles St. Quentin, UMR 1173 (2I), INSERM; Assistance Publique des Hôpitaux de Paris, Paris, France
Olivier Schwartz
Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris; Vaccine Research Institute, Créteil, France

Abstract

Background: First-generation anti-SARS-CoV-2 monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence of resistant Omicron variants. In 2024, 2 novel mAbs, VYD222/Pemivibart and AZD3152/Sipavibart, were approved by health authorities, but their activity against contemporary JN.1 sublineages is poorly characterized. 


Methods: We isolated authentic JN.1.1, KP.1.1, LB.1, and KP.3.3 viruses and evaluated their sensitivity to neutralization by these mAbs in 2 target cell lines. 


Results: Compared to ancestral strains, VYD222/Pemivibart remained moderately active against JN.1 subvariants, with a strong increase of 50% Inhibitory Concentration (IC50), reaching up to 3 to 15 µg/mL for KP.3.3. AZD3152/Sipavibart neutralized JN.1.1 but lost antiviral efficacy against KP.1.1, LB.1, and KP.3.3. 


Conclusions: Our results highlight the need for a close clinical monitoring of VYD222/Pemivibart and raise concerns about the clinical efficacy of AZD3152/Sipavibart.

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Vol. 10 No. 1 (2024): Volume 10, Number 1
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