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骆驼科单域抗体在治疗微生物感染中的应用。

Single domain antibodies from camelids in the treatment of microbial infections.

机构信息

Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium.

VIB-VUB Center for Structural Biology, Vrije Universiteit Brussel, Brussels, Belgium.

出版信息

Front Immunol. 2024 May 17;15:1334829. doi: 10.3389/fimmu.2024.1334829. eCollection 2024.

Abstract

Infectious diseases continue to pose significant global health challenges. In addition to the enduring burdens of ailments like malaria and HIV, the emergence of nosocomial outbreaks driven by antibiotic-resistant pathogens underscores the ongoing threats. Furthermore, recent infectious disease crises, exemplified by the Ebola and SARS-CoV-2 outbreaks, have intensified the pursuit of more effective and efficient diagnostic and therapeutic solutions. Among the promising options, antibodies have garnered significant attention due to their favorable structural characteristics and versatile applications. Notably, nanobodies (Nbs), the smallest functional single-domain antibodies of heavy-chain only antibodies produced by camelids, exhibit remarkable capabilities in stable antigen binding. They offer unique advantages such as ease of expression and modification and enhanced stability, as well as improved hydrophilicity compared to conventional antibody fragments (antigen-binding fragments (Fab) or single-chain variable fragments (scFv)) that can aggregate due to their low solubility. Nanobodies directly target antigen epitopes or can be engineered into multivalent Nbs and Nb-fusion proteins, expanding their therapeutic potential. This review is dedicated to charting the progress in Nb research, particularly those derived from camelids, and highlighting their diverse applications in treating infectious diseases, spanning both human and animal contexts.

摘要

传染病仍然对全球健康构成重大挑战。除了疟疾和艾滋病毒等疾病的持续负担外,抗生素耐药病原体引发的医院感染爆发也突显了持续存在的威胁。此外,最近的传染病危机,如埃博拉和 SARS-CoV-2 爆发,加剧了对更有效和高效的诊断和治疗解决方案的追求。在有前途的选择中,由于其有利的结构特征和多种应用,抗体引起了人们的极大关注。值得注意的是,纳米抗体(Nbs)是由骆驼科产生的仅重链的最小功能性单域抗体,在稳定的抗原结合方面表现出显著的能力。与传统的抗体片段(抗原结合片段(Fab)或单链可变片段(scFv))相比,它们具有易于表达和修饰以及增强的稳定性的独特优势,并且与由于其低溶解度而可能聚集的传统抗体片段(Fab 或 scFv)相比,它们具有更好的亲水性。纳米抗体直接针对抗原表位,或者可以被工程化为多价 Nbs 和 Nb-融合蛋白,从而扩大了它们的治疗潜力。本综述旨在概述 Nb 研究的进展,特别是源自骆驼科的 Nb 研究的进展,并强调它们在治疗传染病方面的多种应用,涵盖人类和动物两个方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cb2/11140111/07a1b6f3f37f/fimmu-15-1334829-g001.jpg

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