Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP.3.3 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
Pathogens and Immunity, doi:10.20411/pai.v10i1.752
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monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence of resistant Omicron variants.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.
AUTHOR CONTRIBUTIONS Experimental strategy design, experiments: DP, IS, CP, FG-B, ES-L, HM, M-ARW, OS. Vital materials: CP, EY, BJ, YR, VE, HM, M-ARW. Phylogenetic analysis: ES-L. Viral sequencing: EY, BJ, YR, VE, MP, FL, ES-L, M-ARW. Manuscript writing and editing: DP, ES-L, HM, M-ARW, OS.
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'abstract': '<jats:p>Background: First-generation anti-SARS-CoV-2 monoclonal antibodies (mAbs) used for '
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'Methods: We isolated authentic JN.1.1, KP.1.1, LB.1, and KP.3.3 viruses and evaluated their '
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'Results: Compared to ancestral strains, VYD222/Pemivibart remained moderately active against '
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'Conclusions: Our results highlight the need for a close clinical monitoring of '
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