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

• Main Authors: Delphine Planas (Author), Isabelle Staropoli (Author), Cyril Planchais (Author), Emilie Yab (Author), Banujaa Jeyarajah (Author), Yannis Rahou (Author), Matthieu Prot (Author), Florence Guivel-Benhassine (Author), Frederic Lemoine (Author), Vincent Enouf (Author), Etienne Simon-Loriere (Author), Hugo Mouquet (Author), Marie-Anne (Author), Olivier Schwartz (Author)
• Format: Book
• Published: Case Western Reserve University, 2024-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence of resistant Omicron variants.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.

Item Description

10.20411/pai.v10i1.752
2469-2964