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从成功的人类疫苗中汲取的经验教训:通过剖析衣壳蛋白来确定关键表位。

Lessons learned from successful human vaccines: Delineating key epitopes by dissecting the capsid proteins.

作者信息

Zhang Xiao, Xin Lu, Li Shaowei, Fang Mujin, Zhang Jun, Xia Ningshao, Zhao Qinjian

机构信息

a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics; National Institute of Diagnostics and Vaccine Development in Infectious Diseases; Xiamen University ; Xiamen , Fujian , PR China.

出版信息

Hum Vaccin Immunother. 2015;11(5):1277-92. doi: 10.1080/21645515.2015.1016675.

DOI:10.1080/21645515.2015.1016675
PMID:25751641
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4514273/
Abstract

Recombinant VLP-based vaccines have been successfully used against 3 diseases caused by viral infections: Hepatitis B, cervical cancer and hepatitis E. The VLP approach is attracting increasing attention in vaccine design and development for human and veterinary use. This review summarizes the clinically relevant epitopes on the VLP antigens in successful human vaccines. These virion-like epitopes, which can be delineated with molecular biology, cryo-electron microscopy and x-ray crystallographic methods, are the prerequisites for these efficacious vaccines to elicit functional antibodies. The critical epitopes and key factors influencing these epitopes are discussed for the HEV, HPV and HBV vaccines. A pentamer (for HPV) or a dimer (for HEV and HBV), rather than a monomer, is the basic building block harboring critical epitopes for the assembly of VLP antigen. The processing and formulation of VLP-based vaccines need to be developed to promote the formation and stabilization of these epitopes in the recombinant antigens. Delineating the critical epitopes is essential for antigen design in the early phase of vaccine development and for critical quality attribute analysis in the commercial phase of vaccine manufacturing.

摘要

基于重组病毒样颗粒(VLP)的疫苗已成功用于预防由病毒感染引起的三种疾病:乙型肝炎、宫颈癌和戊型肝炎。VLP方法在人用和兽用疫苗设计与开发中受到越来越多的关注。本综述总结了成功的人用疫苗中VLP抗原上与临床相关的表位。这些病毒样表位可用分子生物学、冷冻电子显微镜和X射线晶体学方法进行描绘,是这些有效疫苗引发功能性抗体的先决条件。本文讨论了戊型肝炎病毒(HEV)、人乳头瘤病毒(HPV)和乙型肝炎病毒(HBV)疫苗的关键表位以及影响这些表位的关键因素。五聚体(针对HPV)或二聚体(针对HEV和HBV)而非单体,是承载VLP抗原组装关键表位的基本构建单元。需要开发基于VLP的疫苗的加工和配方,以促进这些表位在重组抗原中的形成和稳定。描绘关键表位对于疫苗开发早期阶段的抗原设计以及疫苗生产商业阶段的关键质量属性分析至关重要。

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