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蛋白工程和 B 细胞表位的颗粒展示,以促进新型疫苗的开发。

Protein engineering and particulate display of B-cell epitopes to facilitate development of novel vaccines.

机构信息

Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, United States; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.

Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, United States.

出版信息

Curr Opin Immunol. 2019 Aug;59:49-56. doi: 10.1016/j.coi.2019.03.003. Epub 2019 Apr 28.

Abstract

Induction of antigen-specific humoral immunity is a correlate of protection for many diseases and remains a primary vaccine goal. Pathogens can evade such responses by limiting epitope access, by diversifying surface residues, or by keeping antigens in metastable conformations. B cells can target diverse epitopes on an antigen, but only a subset of which produce functional antibodies. Structure-based immunogen engineering can help overcome these hurdles by using structural information for targeted induction of particular antibodies while improving the overall vaccine immunogenicity. This review will cover recent progress in vaccine design, specifically focusing on strategies to stabilize antigens for optimal B-cell epitope exposure, engineer synthetic B-cell epitopes to induce antibodies with specific features and enhancement of vaccine potency through antigen presentation on multivalent particles.

摘要

诱导抗原特异性体液免疫是许多疾病的保护相关因素,仍然是疫苗的主要目标。病原体可以通过限制表位的可及性、多样化表面残基或使抗原处于亚稳定构象来逃避这种反应。B 细胞可以针对抗原上的多种表位,但只有其中一部分产生功能性抗体。基于结构的免疫原工程可以通过利用结构信息来有针对性地诱导特定的抗体,同时提高疫苗的整体免疫原性,从而帮助克服这些障碍。本综述将介绍疫苗设计的最新进展,特别是侧重于稳定抗原以实现最佳 B 细胞表位暴露的策略、设计合成 B 细胞表位以诱导具有特定特征的抗体,以及通过多价颗粒上的抗原呈递来增强疫苗效力。

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