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

Q1 Medicine

Pathogens and Immunity Pub Date : 2024-09-30 eCollection Date: 2024-01-01 DOI:10.20411/pai.v10i1.752

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

{"title":"Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP3.3 From Approved Monoclonal Antibodies.","authors":"Delphine Planas, Isabelle Staropoli, Cyril Planchais, Emilie Yab, Banujaa Jeyarajah, Yannis Rahou, Matthieu Prot, Florence Guivel-Benhassine, Frederic Lemoine, Vincent Enouf, Etienne Simon-Loriere, Hugo Mouquet, Marie-Anne Rameix-Welti, Olivier Schwartz","doi":"10.20411/pai.v10i1.752","DOIUrl":null,"url":null,"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monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence of resistant Omicron variants.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.","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"10 1","pages":"1-11"},"PeriodicalIF":0.0000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464000/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pathogens and Immunity","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.20411/pai.v10i1.752","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

SARS-CoV-2变体KP.1.1、LB.1和KP3.3从获批的单克隆抗体中逃逸。

背景：用于免疫功能低下患者预防或治疗的第一代抗SARS-CoV-2单克隆抗体（mAbs）因出现耐药的Omicron变种而被撤销。2024 年，2 种新型 mAbs（VYD222/Pemivibart 和 AZD3152/Sipavibart）获得卫生部门批准，但它们对当代 JN.1 亚系的活性特征尚不明确：我们分离了真实的 JN.1.1、KP.1.1、LB.1 和 KP.3.3 病毒，并在 2 个靶细胞系中评估了这些 mAbs 中和病毒的敏感性：结果：与祖先毒株相比，VYD222/Pemivibart对JN.1亚变体仍有中度活性，但50%抑制浓度（IC50）大幅提高，对KP3.3的抑制浓度高达3至15微克/毫升。AZD3152/Sipavibart中和了JN.1.1，但对KP.1.1、LB.1和KP3.3失去了抗病毒效果：我们的研究结果凸显了对 VYD222/Pemivibart 进行密切临床监测的必要性，并引发了对 AZD3152/Sipavibart 临床疗效的担忧。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊