Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP3.3 From Approved Monoclonal Antibodies

Delphine Planas; Isabelle Staropoli; Cyril Planchais; Emilie Yab; Banujaa Jeyarajah; Yannis Rahou; Matthieu Prot; Florence Guivel-Benhassine; Frederic Lemoine; Vincent Enouf; Etienne Simon-Loriere; Hugo Mouquet; Marie-Anne Rameix-Welti; Olivier Schwartz

doi:10.20411/pai.v10i1.752

Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP3.3 From Approved Monoclonal Antibodies

Pathog Immun. 2024 Sep 30;10(1):1-11. doi: 10.20411/pai.v10i1.752. eCollection 2024.

Authors

Delphine Planas^{1

2}, Isabelle Staropoli¹, Cyril Planchais³, Emilie Yab⁴, Banujaa Jeyarajah⁴, Yannis Rahou⁴, Matthieu Prot⁵, Florence Guivel-Benhassine¹, Frederic Lemoine⁶, Vincent Enouf⁴, Etienne Simon-Loriere⁵, Hugo Mouquet³, Marie-Anne Rameix-Welti^{4

7}, Olivier Schwartz^{1

2}

Affiliations

¹ Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France.
² Vaccine Research Institute, Créteil, France.
³ Humoral Immunology Unit, Institut Pasteur, Université Paris Cité, Paris, France.
⁴ National Reference Center for Respiratory Viruses, Molecular Mechanisms of Multiplication of Pneumoviruses Unit, Institut Pasteur, Université Paris Cité, Paris, France.
⁵ G5 Evolutionary Genomics of RNA Viruses, Institut Pasteur, Université Paris Cité, Paris, France.
⁶ Bioinformatics and Biostatistics Hub, Paris, France.
⁷ 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.

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monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence of resistant Omicron variants.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 KP3.3. AZD3152/Sipavibart neutralized JN.1.1 but lost antiviral efficacy against KP.1.1, LB.1, and KP3.3.

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

Keywords: Pemivibart; SARS-CoV-2 variants; Sipavibart; monoclonal antibodies; neutralization.