Camelid Single-Domain Antibodies As an Alternative to Overcome Challenges Related to the Prevention, Detection, and Control of Neglected Tropical Diseases.
Camelid Single-Domain Antibodies As an Alternative to Overcome Challenges Related to the Prevention, Detection, and Control of Neglected Tropical Diseases.
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DOI：
10.3389/fimmu.2017.00653
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发表时间：
2017
影响因子：
7.3
通讯作者：
Stabeli RG
中科院分区：
文献类型：
--
作者：
Fernandes CFC;Pereira SDS;Luiz MB;Zuliani JP;Furtado GP;Stabeli RG
抗体主要由于具有高亲和力和抗原特异性等特性，已成为生物医学研究、诊断和治疗人类多种疾病的重要工具。当目标是给药治疗时，使用策略来降低异源蛋白的免疫原性，并改善药代动力学和药效学特性。尺寸最小化有助于改善这些特性，同时保留抗原-抗体相互作用部位。自从发现骆驼产生不含轻链的功能性抗体以来，研究建议将单一结构域用于生物传感器、肿瘤的监测和治疗、炎症性和神经退行性疾病的治疗、药物输送或被动免疫治疗。尽管预计未来几年药品市场的抗体和相关产品会有所增加，但很少有研究倡议涉及开发替代方案来帮助管理被忽视的热带病(NTDS)。本文就骆驼单域抗体(VHH)在NTDS领域的研究进展作一综述。对VHH衍生产品给予了特别关注，即VHH与纳米颗粒融合，用于开发快速诊断试剂盒；与寡聚基质蛋白融合以用于病毒中和；以及与蛋白质结合用于治疗人类寄生虫。此外，使用VHH的并列转基因技术是控制寄生虫在载体中发展的一种有趣的方法。由于具有巨大的生物技术通用性、异源生产的便利和低成本以及更强的识别不同表位的能力，VHH已成为克服与人类疾病，特别是NTDS的预防、检测和控制有关的挑战的机会。
Due mainly to properties such as high affinity and antigen specificity, antibodies have become important tools for biomedical research, diagnosis, and treatment of several human diseases. When the objective is to administer them for therapy, strategies are used to reduce the heterologous protein immunogenicity and to improve pharmacokinetic and pharmacodynamic characteristics. Size minimization contributes to ameliorate these characteristics, while preserving the antigen–antibody interaction site. Since the discovery that camelids produce functional antibodies devoid of light chains, studies have proposed the use of single domains for biosensors, monitoring and treatment of tumors, therapies for inflammatory and neurodegenerative diseases, drug delivery, or passive immunotherapy. Despite an expected increase in antibody and related products in the pharmaceutical market over the next years, few research initiatives are related to the development of alternatives for helping to manage neglected tropical diseases (NTDs). In this review, we summarize developments of camelid single-domain antibodies (VHH) in the field of NTDs. Particular attention is given to VHH-derived products, i.e., VHHs fused to nanoparticles, constructed for the development of rapid diagnostic kits; fused to oligomeric matrix proteins for viral neutralization; and conjugated with proteins for the treatment of human parasites. Moreover, paratransgenesis technology using VHHs is an interesting approach to control parasite development in vectors. With enormous biotechnological versatility, facility and low cost for heterologous production, and greater ability to recognize different epitopes, VHHs have appeared as an opportunity to overcome challenges related to the prevention, detection, and control of human diseases, especially NTDs.