Neutralization of recent SARS-CoV-2 variants by genetically and structurally related mAbs of the pemivibart lineage

Abstract

Pemivibart is a monoclonal antibody therapy currently under Emergency Use Authorization for the for the pre-exposure prophylaxis of coronavirus disease 2019 (COVID-19) in adults and adolescents over 12 years of age with certain immunocompromised conditions. As a part of the overall monitoring strategy for the activity of pemivibart, the antibody is regularly evaluated against emerging variants of SARS-CoV-2 using pseudovirus neutralization assays. Recent clinical data from Invivyd demonstrates that the PhenoSense pseudovirus assays carried out at Monogram Biosciences have been a reliable and consistent predictor of continued pemivibart clinical activity against SARS-COV-2 variants that have predominated across the timespan that includes the CANOPY clinical trial and the post-EUA authorization period. Additionally, new potential antibodies based upon the structural framework of pemivibart are continuously under evaluation. Fifteen of these yeast-produced "pemivibart-like" antibodies were tested for neutralization activity against recent variants KP.3 and KP.3.1.1. Like pemivibart, all 15 maintained activity against KP.3.1.1, with the change in IC50 averaging 2.51-fold +/-0.7 compared to KP.3. Four pemivibart-like antibodies were also tested against the XEC variant, with the change in IC50 averaging 3.01-fold compared to KP.3. These data suggest continued activity for pemivibart and pemivibart-like antibodies against KP.3.1.1 and XEC, recent variants containing N-terminal domain modifications.