Neutralizing Activity and Viral Escape of Pemivibart by SARS-CoV-2 JN.1 sublineages
Tianjiao Yao, Zhenghai Ma, Ke Lan, Yicheng Guo, Lihong Liu
doi:10.1101/2024.11.08.622746
Pemivibart (Pemgarda™/VYD222) was granted Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA) on March 22, 2024, for COVID-19 pre-exposure prophylaxis in immunocompromised individuals. However, its efficacy and resistance against JN.1 sublineages have yet to be fully characterized. Here, we first assessed the neutralizing activity of Pemivibart against a panel of VSV-based pseudoviruses representing contemporary JN.1 sublineages, including XEC, the fastest-growing SARS-CoV-2 strain globally, in both Vero-E6 and Vero-E6-TMPRSS2-T2A-hACE2 (Vero-E6-TA) cells. We then engineered a replicationcompetent vesicular stomatitis virus with JN.1 spike (rVSVΔG-JN.1) to select for escape variants and performed structural analyses to comprehensively map Pemivibart's escape mutations. Our results demonstrated that Pemivibart exhibited comparable neutralization patterns in both cell lines and retains broad effectiveness against SARS-CoV-2 JN.1 sublineages tested. However, its potency was remarkably reduced against KP.3.1.1 and XEC, with IC50 values of approximately 4.2 µg/mL, about 22-fold higher than that for JN.1, as well as JN.1-derived Pemivibart-escape mutants harbouring low-frequency mutations across SARS-CoV-2 strains through mutiple antibody evasion mechanisms in Vero-E6-TA cells. Collectively, our findings underscored the importance of monitoring the clinical efficacy of Pemivibart as JN.1 sublineages continue to evolve. The escape profile of Pemivibart could provide valuable insights for forecasting and optimizing its effectiveness against emerging SARS-CoV-2 variants.
References
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Planas, Staropoli, Planchais, Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP3.3 From Approved Monoclonal Antibodies, Pathog Immun
Wang, Guo, Ho, Ho, Pemivibart is less active against recent SARS-CoV-2 JN.1 sublineages, bioRxiv
Yisimayi, Song, Wang, Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting, Nature
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'abstract': '<jats:p>Pemivibart (Pemgarda/VYD222) was granted Emergency Use Authorization (EUA) by the '
'U.S. Food and Drug Administration (FDA) on March 22, 2024, for COVID-19 pre-exposure '
'prophylaxis in immunocompromised individuals. However, its efficacy and resistance against '
'JN.1 sublineages have yet to be fully characterized. Here, we first assessed the neutralizing '
'activity of Pemivibart against a panel of VSV-based pseudoviruses representing contemporary '
'JN.1 sublineages, including XEC, the fastest-growing SARS-CoV-2 strain globally, in both '
'Vero-E6 and Vero-E6-TMPRSS2-T2A-hACE2 (Vero-E6-TA) cells. We then engineered a '
'replication-competent vesicular stomatitis virus with JN.1 spike (rVSVΔG-JN.1) to select for '
"escape variants and performed structural analyses to comprehensively map Pemivibart's escape "
'mutations. Our results demonstrated that Pemivibart exhibited comparable neutralization '
'patterns in both cell lines and retains broad effectiveness against SARS-CoV-2 JN.1 '
'sublineages tested. However, its potency was remarkably reduced against KP.3.1.1 and XEC, '
'with IC50 values of approximately 4.2 μg/mL, about 22-fold higher than that for JN.1, as well '
'as JN.1-derived Pemivibart-escape mutants harbouring low-frequency mutations across '
'SARS-CoV-2 strains through mutiple antibody evasion mechanisms in Vero-E6-TA cells. '
'Collectively, our findings underscored the importance of monitoring the clinical efficacy of '
'Pemivibart as JN.1 sublineages continue to evolve. The escape profile of Pemivibart could '
'provide valuable insights for forecasting and optimizing its effectiveness against emerging '
'SARS-CoV-2 variants.</jats:p>',
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'title': 'Neutralizing Activity and Viral Escape of Pemivibart by SARS-CoV-2 JN.1 sublineages',
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