案例信息

标题：手足口病相关肠道病毒广谱中和表位发现及疫苗研究

【专业学位类别】公共卫生

【专业领域/方向】转化医学

【作者】徐龙发

【单位】厦门大学公共卫生学院

【关键词】手足口病、肠道病毒、广谱中和表位、疫苗

【适用课程】流行病学、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】

手足口病（HFMD）是我国当前重要的公共卫生问题，其病原体包括了多种不同血清型的肠道病毒。发现广谱抗病毒表位对于开展新型广谱疫苗和治疗药物研究具有重要意义。不同型别肠道病毒具有相似的病毒颗粒脱衣壳及核酸释放过程，其中可能存在较为高度保守的中间态隐匿结构域，是发现广谱抗病毒表位的理想靶标。该研究通过构建可靶向脱衣壳中间态的新型广谱中和抗体，应用序贯免疫，不同中间态结合ELISA及快速高通量中和抗体检测方法，获得了靶向中间态隐匿结构域的广谱抗病毒表位精确信息与效应抗体分子，综合应用结构生物学和生物信息学对获得的不同血清型病毒中和表位的结构信息开展表位特征聚类分析，并通过动物实验，指导筛选能够诱导较优广谱免疫原性的颗粒抗原。通过解读该研究的关键环节，使学生掌握肠道病毒广谱中和抗体发现及指导广谱疫苗筛选设计研究方法的基本概念，学习方案设计与实施，培养学生开展病毒的广谱中和表位发现及疫苗评价能力。

Title: Discovery of Broad-Spectrum Neutralizing Epitopes of Enterovirus Associated with Hand, Foot, and Mouth Disease (HFMD) and Vaccine Research

Professional Degree Category: Master of Public Health

Specialized fields: Translational Medicine

Authors: Longfa Xu

Affiliation: School of Public Health, Xiamen University

Key words: Hand, foot, and mouth disease, Enterovirus, Broad-spectrum neutralizing epitope, Vaccine

Abstract

Hand, foot, and mouth disease (HFMD) is an important public health issue currently, with its pathogens including many different serotypes of enteroviruses. The discovery of broad-spectrum antiviral epitopes is crucial for the development of new broad-spectrum vaccines and therapeutic drugs. Different types of enteroviruses have similar viral particle uncoating and nucleic acid release processes, among which there may exist highly conserved intermediate state cryptic structural domains, making them ideal targets for broad-spectrum antiviral epitope discovery. This research obtained precise information on broad-spectrum antiviral epitopes targeting the cryptic structural domains in the intermediate state and the effector antibody molecules by constructing a new broad-spectrum neutralizing antibody that can target the uncoating intermediate state, applying sequential immunization, different intermediate state binding ELISA and rapid high-throughput neutralizing antibody detection methods. The structural information of the neutralizing epitopes of different serotypes of viruses was also analyzed for epitope characteristics clustering, integrating structural biology and bioinformatics. Additionally, particle antigens that can induce superior broad-spectrum immunogenicity were guided and selected through animal experiments. By interpreting the key steps of this study, students will grasp the basic concepts of the discovery of enterovirus broad-spectrum neutralizing antibodies and the research methods for guiding broad-spectrum vaccine screening and design, learn about the design and implementation of plans, and cultivate the ability to conduct broad-spectrum neutralizing epitope discovery and vaccine evaluation for viruses.

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