Neutralization of recent SARS-CoV-2 variants by genetically and structurally related mAbs of the pemivibart lineage
Colin Powers, Braedon Williams, Alex Kreher, Feng Gao, Brandyn West, Daniel Chupp, Robert Allen
doi:10.1101/2024.11.11.623127
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.
References
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doi:10.1101/2024.11.08.622746{ 'institution': [{'name': 'bioRxiv'}],
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'abstract': '<jats:p>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.</jats:p>',
'DOI': '10.1101/2024.11.11.623127',
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'title': [ 'Neutralization of recent SARS-CoV-2 variants by genetically and structurally related mAbs of '
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{'given': 'Feng', 'family': 'Gao', 'sequence': 'additional', 'affiliation': []},
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