轮状病毒是导致婴幼儿腹泻的主要病原体，造成严重的社会经济负担。安全有效的疫苗是控制轮状病毒的重要手段，但现有减毒活疫苗在轮状病毒导致的死亡率较高的非洲和亚洲部分地区的有效性均较低。发展更加高效的疫苗才能进一步降低轮状病毒感染导致的婴幼儿死亡率。感染婴幼儿的轮状病毒超过13个P基因型，交叉中和表位及其中和机制的研究可以为研制更加高效、广谱的轮状病毒疫苗提供依据。目前，已发现的交叉中和抗体大部分识别VP5，但其交叉中和机制仍不清楚。本课题组在前期工作中发现截短表达的VP4有望成为轮状病毒候选疫苗，其免疫血清具有交叉中和活性，并已筛选获得多株交叉中和单抗。本项目拟在前期工作的基础上，通过解析交叉中和抗体与轮状病毒免疫复合物的结构以及逃逸突变、定点突变等技术研究VP4蛋白交叉中和表位特征，结合生物学功能研究和表位信息，阐明VP4抗体的交叉中和机制，为研究更加高效的轮状病毒疫苗提供依据。

Globally, group A rotaviruses are the leading causes of diarrhea in infants and young children, resulting in serious social and economic burden. Vaccination is the most efficient strategy for prevention of rotavirus. However, currently available live attenuated rotavirus vaccines are less effective in some developing countries in Africa and Asia, where most rotavirus related mortality occur and rotavirus vaccines are most critical for saving lives. Thus, it needs to develop more effective rotavirus vaccines to reduce rotavirus induced mortality in these areas. Till now, it has been found that at least 13 P genotypes of rotavirus can infect infants and young children. Thus, the study of cross-neutralizing epitopes and their neutralizing mechanism may provide basis for developing more efficient and broad-spectrum rotavirus vaccines. Most identified cross neutralizing monoclonal antibodies were specific for VP5, however, due to the lack of antigen-antibody complex, the definite epitopes of these cross-neutralizing monoclonal antibodies are still unclear, and the neutralizing mechanism also needs more research. In previous studies, we have found that truncated expressed VP4 could become a potential candidate for rotavirus vaccines, and could stimulate cross-neutralizing antibodies. In addition, 3 cross-neutralizing monoclonal antibodies have been screened by immunization with the truncated VP4. In this study, we would like to map the cross-neutralizing epitopes on VP4 by structural analysis of the antigen-antibody complex, escape mutation and site-directed alanine mutation. In addition, the neutralizing mechanism of these antibodies will be explored by the combination of biological functions and the epitope information. This work will provide basis for the development of more efficient rotavirus vaccines.