Development and characterization of a novel neutralizing scFv vectored immunoprophylaxis against botulinum toxin type A.

IF 4.3 4区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Targeting Pub Date : 2024-12-01 Epub Date: 2024-02-01 DOI:10.1080/1061186X.2023.2301418

Yongpeng Wei, Guangyao Li, Zhuo Wang, Kewen Qian, Shuyi Zhang, Lingling Zhang, Changhai Lei, Shi Hu

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引用次数: 0

Abstract

Botulinum toxin is a protein toxin secreted by Clostridium botulinum that is strongly neurotoxic. Due to its characteristics of being super toxic, quick acting, and difficult to prevent, the currently reported antiviral studies focusing on monoclonal antibodies have limited effectiveness. Therefore, for the sake of effectively prevention and treatment of botulism and to maintain country biosecurity as well as the health of the population, in this study, we intend to establish a single chain antibody (scFv) targeting the carboxyl terminal binding functional domain of the botulinum neurotoxin heavy chain (BONT/AHc) of botulinum neurotoxin type A, and explore the value of a new passive immune method in antiviral research which based on adeno-associated virus (AAV) mediated vector immunoprophylaxis (VIP) strategy. The scFv small-molecular single-chain antibody sequenced, designed, constructed, expressed and purified by hybridoma has high neutralising activity and affinity level, which can lay a good foundation for the modification and development of antibody engineering drugs. In vivo experiments, AAV-mediated scFv engineering drug has good anti-BONT/A toxin neutralisation ability, has advantages of simple operation, stable expression and good efficacy, and may be one of the effective treatment strategies for long-term prevention and protection of BONT/A botulinum neurotoxin.

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针对 A 型肉毒杆菌毒素的新型中和 scFv 病毒载体免疫预防剂的开发和特性鉴定。

肉毒杆菌毒素是由肉毒杆菌分泌的一种蛋白质毒素，具有强烈的神经毒性。由于其毒性超强、起效迅速、难以预防等特点，目前报道的以单克隆抗体为主的抗病毒研究效果有限。因此，为了有效预防和治疗肉毒中毒，维护国家生物安全和人民健康，本研究拟建立针对 A 型肉毒杆菌神经毒素重链（BONT/AHc）羧基末端结合功能域的单链抗体（scFv）、并探索一种基于腺相关病毒（AAV）介导的载体免疫预防（VIP）策略的新型被动免疫方法在抗病毒研究中的价值。通过杂交瘤测序、设计、构建、表达和纯化的 scFv 小分子单链抗体具有较高的中和活性和亲和力，可为抗体工程药物的改造和开发奠定良好的基础。在体内实验中，AAV介导的scFv工程药物具有良好的抗BONT/A毒素中和能力，具有操作简单、表达稳定、疗效好等优点，可作为长期预防和保护BONT/A肉毒杆菌神经毒素的有效治疗策略之一。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Drug Targeting 医学-药学

CiteScore

9.10

自引率

0.00%

发文量

165

审稿时长

2 months

期刊介绍： Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs. Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.