National Key Laboratory of Veterinary Public Health Security, Beijing Key Laboratory of Detection Technology for Animal-Derived Food, College of Veterinary Medicine, China Agricultural University, 100193 Beijing, People's Republic of China.
National Key Laboratory of Veterinary Public Health Security, Beijing Key Laboratory of Detection Technology for Animal-Derived Food, College of Veterinary Medicine, China Agricultural University, 100193 Beijing, People's Republic of China.
Biotechnol Adv. 2023 Jul-Aug;65:108143. doi: 10.1016/j.biotechadv.2023.108143. Epub 2023 Apr 5.
Although the efficacy and commercial success of vaccines and therapeutic antibodies have been tremendous, designing and discovering new drug candidates remains a labor-, time- and cost-intensive endeavor with high risks. The main challenges of vaccine development are inducing a strong immune response in broad populations and providing effective prevention against a group of highly variable pathogens. Meanwhile, antibody discovery faces several great obstacles, especially the blindness in antibody screening and the unpredictability of the developability and druggability of antibody drugs. These challenges are largely due to poorly understanding of germline antibodies and the antibody responses to pathogen invasions. Thanks to the recent developments in high-throughput sequencing and structural biology, we have gained insight into the germline immunoglobulin (Ig) genes and germline antibodies and then the germline antibody features associated with antigens and disease manifestation. In this review, we firstly outline the broad associations between germline antibodies and antigens. Moreover, we comprehensively review the recent applications of antigen-specific germline antibody features, physicochemical properties-associated germline antibody features, and disease manifestation-associated germline antibody features on vaccine development, antibody discovery, antibody optimization, and disease diagnosis. Lastly, we discuss the bottlenecks and perspectives of current and potential applications of germline antibody features in the biotechnology field.
尽管疫苗和治疗性抗体在疗效和商业上取得了巨大成功，但设计和发现新的药物候选物仍然是一项劳动密集型、耗时且成本高昂的工作，风险很高。疫苗开发的主要挑战是在广泛的人群中诱导强烈的免疫反应，并提供针对一组高度变异病原体的有效预防。同时，抗体发现面临着几个巨大的障碍，特别是在抗体筛选中的盲目性，以及抗体药物的可开发性和可成药性的不可预测性。这些挑战在很大程度上是由于对胚系抗体和针对病原体入侵的抗体反应缺乏了解。得益于高通量测序和结构生物学的最新发展，我们深入了解了胚系免疫球蛋白 (Ig) 基因和胚系抗体，然后了解了与抗原和疾病表现相关的胚系抗体特征。在这篇综述中，我们首先概述了胚系抗体与抗原之间的广泛关联。此外，我们全面回顾了抗原特异性胚系抗体特征、与理化性质相关的胚系抗体特征以及与疾病表现相关的胚系抗体特征在疫苗开发、抗体发现、抗体优化和疾病诊断方面的最新应用。最后，我们讨论了当前和潜在应用中胚系抗体特征在生物技术领域的应用的瓶颈和展望。
