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严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变异株KP.1.1、LB.1和KP3.3对已获批单克隆抗体产生逃逸

Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP3.3 From Approved Monoclonal Antibodies.

作者信息

Planas Delphine, Staropoli Isabelle, Planchais Cyril, Yab Emilie, Jeyarajah Banujaa, Rahou Yannis, Prot Matthieu, Guivel-Benhassine Florence, Lemoine Frederic, Enouf Vincent, Simon-Loriere Etienne, Mouquet Hugo, Rameix-Welti Marie-Anne, Schwartz Olivier

机构信息

Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France.

Vaccine Research Institute, Créteil, France.

出版信息

Pathog Immun. 2024 Sep 30;10(1):1-11. doi: 10.20411/pai.v10i1.752. eCollection 2024.

DOI:10.20411/pai.v10i1.752
PMID:39391808
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11464000/
Abstract

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monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence of resistant Omicron variants.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 KP3.3. AZD3152/Sipavibart neutralized JN.1.1 but lost antiviral efficacy against KP.1.1, LB.1, and KP3.3.

CONCLUSIONS

Our results highlight the need for a close clinical monitoring of VYD222/Pemivibart and raise concerns about the clinical efficacy of AZD3152/Sipavibart.

摘要

背景

用于免疫功能低下患者预防或治疗目的的第一代抗SARS-CoV-2单克隆抗体（mAbs）已因耐药奥密克戎变体的出现而被撤回。2024年，两种新型单克隆抗体VYD222/佩米维巴特和AZD3152/西帕维巴特获得卫生当局批准，但它们对当代JN.1亚系的活性特征尚不明确。

方法

我们分离出了正宗的JN.1.1、KP.1.1、LB.1和KP.3.3病毒，并在两种靶细胞系中评估了这些单克隆抗体对它们的中和敏感性。

结果

与原始毒株相比，VYD222/佩米维巴特对JN.1亚变体仍保持适度活性，50%抑制浓度（IC50）大幅增加，对KP3.3高达3至15μg/mL。AZD3152/西帕维巴特可中和JN.1.1，但对KP.1.1、LB.1和KP3.3失去抗病毒效力。

结论

我们的结果凸显了对VYD222/佩米维巴特进行密切临床监测的必要性，并引发了对AZD3152/西帕维巴特临床疗效的担忧。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807e/11464000/c8e206da5f7c/pai-10-001-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807e/11464000/85490b7fd8b3/pai-10-001-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807e/11464000/c8e206da5f7c/pai-10-001-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807e/11464000/85490b7fd8b3/pai-10-001-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/807e/11464000/c8e206da5f7c/pai-10-001-g002.jpg

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