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单域抗体在细菌感染诊断和中和中的应用。

Single Domain Antibody application in bacterial infection diagnosis and neutralization.

机构信息

Department of General Surgery, Center for Microbiome Research of Med-X Institute, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.

The Key Laboratory of Environment and Genes Related to Disease of Ministry of Education, Health Science Center, Xi'an Jiaotong University, Xi'an, China.

出版信息

Front Immunol. 2022 Sep 29;13:1014377. doi: 10.3389/fimmu.2022.1014377. eCollection 2022.

Abstract

Increasing antibiotic resistance to bacterial infections causes a serious threat to human health. Efficient detection and treatment strategies are the keys to preventing and reducing bacterial infections. Due to the high affinity and antigen specificity, antibodies have become an important tool for diagnosis and treatment of various human diseases. In addition to conventional antibodies, a unique class of "heavy-chain-only" antibodies (HCAbs) were found in the serum of camelids and sharks. HCAbs binds to the antigen through only one variable domain Referred to as VHH (variable domain of the heavy chain of HCAbs). The recombinant format of the VHH is also called single domain antibody (sdAb) or nanobody (Nb). Sharks might also have an ancestor HCAb from where SdAbs or V-NAR might be engineered. Compared with traditional Abs, Nbs have several outstanding properties such as small size, high stability, strong antigen-binding affinity, high solubility and low immunogenicity. Furthermore, they are expressed at low cost in microorganisms and amenable to engineering. These superior properties make Nbs a highly desired alternative to conventional antibodies, which are extensively employed in structural biology, unravelling biochemical mechanisms, molecular imaging, diagnosis and treatment of diseases. In this review, we summarized recent progress of nanobody-based approaches in diagnosis and neutralization of bacterial infection and further discussed the challenges of Nbs in these fields.

摘要

细菌感染的抗生素耐药性不断增加,对人类健康构成严重威胁。有效的检测和治疗策略是预防和减少细菌感染的关键。由于抗体具有高亲和力和抗原特异性,因此已成为诊断和治疗各种人类疾病的重要工具。除了常规抗体外,在骆驼和鲨鱼的血清中还发现了一类独特的“重链仅有”抗体(HCAb)。HCAb 通过仅一个可变结构域与抗原结合,称为 VHH(HCAb 的重链可变结构域)。VHH 的重组形式也称为单域抗体(sdAb)或纳米抗体(Nb)。鲨鱼可能也有一个祖先 HCAb,从中可以设计出 SdAbs 或 V-NAR。与传统抗体相比,Nb 具有几个突出的特性,如体积小、稳定性强、抗原结合亲和力强、溶解度高和免疫原性低。此外,它们可以在微生物中以低成本表达,并且易于工程化。这些卓越的特性使 Nb 成为传统抗体的理想替代品,传统抗体广泛用于结构生物学、揭示生化机制、分子成像、疾病诊断和治疗。在这篇综述中,我们总结了基于纳米抗体的方法在细菌感染诊断和中和方面的最新进展,并进一步讨论了 Nb 在这些领域面临的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5246/9558170/886c4fcf395d/fimmu-13-1014377-g001.jpg

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