Escape of SARS-CoV-2 variants KP1.1, LB.1 and KP3.3 from approved monoclonal antibodies

Abstract

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monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence of resistant Omicron variants.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, two novel mAbs, Pemivibart and Sipavibart, have been approved by health authorities, but their activity against contemporary JN.1 sublineages is poorly characterized. We isolated authentic JN.1.1, KP1.1, LB.1 and KP3.3 viruses and evaluated their sensitivity to neutralization by these mAbs in two target cell lines. Compared to ancestral strains, Pemivibart remained moderately active against JN.1 sub-variants, with a strong increase of 50% Inhibitory Concentration (IC50), reaching up to 3 to 15 ug/ml for KP3.3. Sipavibart neutralized JN.1.1 but lost antiviral efficacy against KP1.1, LB.1 and KP3.3. Our results highlight the need for a close clinical monitoring of Pemivibart and raise concerns about the clinical efficacy of Sipavibart.