案例信息

标题：水痘-带状疱疹病毒关键毒力因子发现与新型疫苗研究

【专业学位类别】公共卫生

【专业领域/方向】转化医学、疫苗

【作者】王玮

【单位】厦门大学公共卫生学院

【关键词】毒力因子、疫苗、水痘-带状疱疹病毒、水痘、带状疱疹

【适用课程】转化医学、生物制品学

【版权说明】真实性案例，仅用于教学目的

【案例摘要】

水痘-带状疱疹病毒（VZV）感染引起的水痘与带状疱疹在全球造成了较大的疾病负担。目前，由VZV减毒活疫苗Oka株（vOka）组成的水痘疫苗和带状疱疹疫苗通常是安全有效的。但是在接种者中陆续发现由vOka株导致的带状疱疹病例，相关研究也证明了vOka为混合毒株且仍具有神经感染与潜伏能力，这说明vOka存在导致疫苗株相关带状疱疹的安全隐患。因此，研制新一代更安全的水痘减毒活疫苗将有助于提高人们对水痘疫苗的接受程度，从而更好地建立水痘的人群免疫屏障。本单位联合美国罗格斯大学新泽西医学院首次鉴定出VZV皮肤与神经双毒力的决定因子ORF7，进而构建了首个具有皮肤与神经双减毒性能的新型水痘减毒活疫苗VZV-7D，并应用多种体内外模型系统验证了该疫苗的临床前安全性与免疫原性，为该疫苗进入临床试验提供重要支持。该研究也可为基于功能基因组学与反向遗传学技术研制新型病毒疫苗提供线索与思路。

Title: Identification of Key Virulence Factors of Varicella-Zoster Virus and Development of Novel Vaccines

Professional Degree Category: Master of Public Health

Specialized fields: Translational Medicine，vaccine

Authors: Wei Wang

Affiliation: School of Public Health, Xiamen University

Key words: Virulence factor; Vaccine; VZV; Varicella; Zoster

Abstract

Varicella-zoster virus (VZV) infection causes significant disease burden worldwide in the form of chickenpox and shingles. Currently, the varicella vaccine and shingles vaccine, both composed of the attenuated VZV Oka strain (vOka), are generally safe and effective. However, cases of shingles caused by vOka have been reported in vaccine recipients, and research has shown that vOka is a mixed strain that still retains neuro-virulent and latency capabilities, indicating potential safety concerns related to vaccine-related shingles. Therefore, developing a new generation of safer attenuated VZV vaccines could improve acceptance of the varicella vaccine and better establish herd immunity against chickenpox. Our group, in collaboration with Rutgers New Jersey Medical School, identified for the first dual determinant of VZV skin- and neuro-virulence, ORF7, and constructed a novel attenuated VZV vaccine, VZV-7D, with dual skin and neuroattenuation. The safety and immunogenicity of this vaccine were validated using various in vitro and in vivo models, providing important support for its clinical development. This work could provide in-sights into the research of novel virus vaccines based on functional genomics and reverse genetics.

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