Hybridoma-derived neutralizing monoclonal antibodies against Beta and Delta variants of SARS-CoV-2 in vivo
作者机构：State Key Laboratory of VirologyWuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China State Key Laboratory of Medicinal Chemical BiologyCollege of Life SciencesNankai UniversityTianjin300071China Department of Forensic MedicineTongji Medical College of Huazhong University of Science and TechnologyWuhan430010China Hubei Jiangxia LaboratoryWuhan430200China
出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)
年 卷 期：2023年第38卷第2期
页 面：257-267页
核心收录：
学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学]
基 金：supported by grants from the National Key R&D Program of China(2021YFC2301700) National Natural Science Foundation of China(82061138021) the Key Biosafety Science and Technology Program of Hubei Jiangxia Laboratory(JXBS001) Hubei Natural Science Foundation for Distinguished Young Scholars(2021CFA050)
主 题：COVID-19 SARS-CoV-2 B.1.351 B.1.617.2 Monoclonal antibody
摘 要：Neutralizing monoclonal antibodies(mAb)are a major therapeutic strategy for the treatment of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)*** continuous emergence of new SARS-CoV-2 variants worldwide has increased the urgency for the development of new *** this study,we immunized mice with the receptor-binding domain(RBD)of the SARS-CoV-2 prototypic strain(WIV04)and screened 35 RBDspecific mAbs using hybridoma *** of the plaque reduction neutralization test showed that 25 of the mAbs neutralized authentic WIV04 strain *** 25 mAbs were divided into three categories based on the competitive enzyme-linked immunosorbent assay results.A representative mAb was selected from each category(RD4,RD10,and RD14)to determine the binding kinetics and median inhibitory concentration(IC_(50))of WIV04 and two variants of concern(VOC):B.1.351(Beta)and B.1.617.2(Delta).RD4 neutralized the B.1.617.2 variant with an IC50 of 2.67 ng/mL;however,it completely lost neutralizing activity against the B.1.351 ***10 neutralized both variants with an IC50 exceeding 100 ng/mL;whereas RD14 neutralized two variants with a higher IC50(1 mg/mL).Animal experiments were performed to evaluate the protective effects of RD4 and RD10 against various VOC ***4 could protect Adv-hACE2 transduced mice from B.1.617.2 infection at an antibody concentration of 25 mg/kg,while RD10 could protect mice from B.1.351 infection at an antibody concentration of 75 mg/*** results highlight the potential for future modifications of the mAbs for practical use.
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