人肠道病毒引发的传染性疾病带来严重健康威胁，包括肠道病毒71型（EV71）、柯萨奇病毒A16型(CVA16)和A6型(CVA6)等引发的手足口病和埃可病毒30型(EC30)相关的婴幼儿脑膜炎，目前尚无批准药物和疫苗。我们已在酿酒酵母中建立了EV71病毒样颗粒（VLP）的自组装体系，验证了其免疫原性和免疫保护作用；通过SP70表位氨基酸序列置换得到了EV71/CVA16嵌合VLP，验证了该嵌合VLP能提供针对EV71和CVA16的双重保护作用。本课题将：1）解析EV71/CVA16嵌合VLP的高分辨结构，揭示中和机制的结构学基础；2）以EV71-VLP或EV71/CVA16嵌合VLP为平台在SP70表位置换或插入CVA6等其它手足口病相关肠道病毒或者EC30等中和表位，研究其免疫保护作用和高分辨结构。本课题探索获得具广谱肠道病毒保护作用的重组VLP，为创新治疗手段开发提供依据。

Infectious diseases associated with enterovirus infection have caused significant morbidity and mortality in infants. These causative agents include enterovirus 71 (EV71)、coxsackievirus A16 (CVA16) and A6 (CVA6) responsible for hand-foot-and-mouth-disease (HFMD), echovirus 30 associated with aseptic meningitis. So far drugs and vaccines are unavailable for HFMD and aseptic meningitis. Previously we have developed Saccharomyces cerevisiae into a high level expression system for production of EV71 virus-like particles (VLPs) and demonstrated the immunogenicity and immune protection effects of these EV71-VLPs; by the substitution of SP70 neutralization epitope in EV71 capsid protein VP1 with corresponding resides from CVA16, we have obtained EV71/CVA16 chimeric VLPs shown to be able to confer protection against both EV71 and CVA16 infections. We will 1) determine the structures of EV71/CVA16 chimeric VLP and elucidate the structural basis of immunogenicity; 2) present the neutralization epitopes of other HFMD-associated enteroviruses such as CVA6 and then those of EC30 using the EV71 VLP or EV71/CVA16-VLP as the platform, followed by immunology and structure studies. The aim of this project is to produce broad spectrum anti-enterovirus vaccine candidates for novel therapeutics development.