基于 CR3022 产生的针对 SARS-CoV-2 奥密克戎变异株的中和双特异性单链抗体
A neutralizing bispecific single-chain antibody against SARS-CoV-2 Omicron variant produced based on CR3022.
机构信息
Changchun Veterinary Research Institute, Chinese Academy of Agricultural Science, Changchun, Jilin, China.
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
出版信息
Front Cell Infect Microbiol. 2023 May 3;13:1155293. doi: 10.3389/fcimb.2023.1155293. eCollection 2023.
INTRODUCTION
The constantly mutating SARS-CoV-2 has been infected an increasing number of people, hence the safe and efficacious treatment are urgently needed to combat the COVID-19 pandemic. Currently, neutralizing antibodies (Nabs), targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein are potentially effective therapeutics against COVID-19. As a new form of antibody, bispecific single chain antibodies (BscAbs) can be easily expressed in and exhibits broad-spectrum antiviral activity.
METHODS
In this study, we constructed two BscAbs 16-29, 16-3022 and three single chain variable fragments (scFv) S1-16, S2-29 and S3022 as a comparison to explore their antiviral activity against SARS-CoV-2. The affinity of the five antibodies was characterized by ELISA and SPR and the neutralizing activity of them was analyzed using pseudovirus or authentic virus neutralization assay. Bioinformatics and competitive ELISA methods were used to identify different epitopes on RBD.
RESULTS
Our results revealed the potent neutralizing activity of two BscAbs 16-29 and 16-3022 against SARS-CoV-2 original strain and Omicron variant infection. In addition, we also found that SARS-CoV RBD-targeted scFv S3022 could play a synergistic role with other SARS-CoV-2 RBD-targeted antibodies to enhance neutralizing activity in the form of a BscAb or in cocktail therapies.
DISCUSSION
This innovative approach offers a promising avenue for the development of subsequent antibody therapies against SARSCoV-2. Combining the advantages of cocktails and single-molecule strategies, BscAb therapy has the potential to be developed as an effective immunotherapeutic for clinical use to mitigate the ongoing pandemic.
简介
不断变异的 SARS-CoV-2 已感染了越来越多的人，因此急需安全有效的治疗方法来应对 COVID-19 大流行。目前，针对 SARS-CoV-2 刺突蛋白受体结合域（RBD）的中和抗体（Nabs）是治疗 COVID-19 的潜在有效疗法。作为一种新型抗体，双特异性单链抗体（BscAbs）可以在 中轻松表达，并表现出广谱抗病毒活性。
方法
在这项研究中，我们构建了两种 BscAbs 16-29、16-3022 和三种单链可变片段（scFv）S1-16、S2-29 和 S3022 作为比较，以探索它们对 SARS-CoV-2 的抗病毒活性。通过 ELISA 和 SPR 对五种抗体的亲和力进行了表征，并通过假病毒或真实病毒中和测定分析了它们的中和活性。生物信息学和竞争性 ELISA 方法用于鉴定 RBD 上的不同表位。
结果
我们的结果显示，两种 BscAbs 16-29 和 16-3022 对 SARS-CoV-2 原始株和奥密克戎变异株感染具有强大的中和活性。此外，我们还发现，SARS-CoV RBD 靶向 scFv S3022 可以与其他 SARS-CoV-2 RBD 靶向抗体协同作用，以 BscAb 或鸡尾酒疗法的形式增强中和活性。
讨论
这种创新方法为开发针对 SARSCoV-2 的后续抗体疗法提供了有前途的途径。BscAb 疗法结合了鸡尾酒和单分子策略的优势，有可能被开发为临床使用的有效免疫疗法，以减轻当前的大流行。
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