引发病毒原位崩解的新型中和抗体的免疫原诱导机制研究

疫苗的发明和使用是人类医学史上最突出的成就之一，特别是在病毒性传染病中，疫苗诱导有效的中和抗体应答，是预防病毒感染最有效手段。本课题组在前期对戊肝病毒的研究中发现了一类全新的中和抗体。不同于经典中和抗体，这类新型抗体无需其他免疫系统成员的参与就可以诱导病毒原位崩解，使病毒直接失活。这类抗体及表位的发现将为一些经典抗体表位高度突变或难以诱导稳定抗体应答的病原体（如流感病毒、艾滋病毒）的疫苗研究提供全新的思路。但这类抗体的作用机理和诱导机制尚不清楚。进一步，我们还发现一些重组的颗粒性抗原较于天然病原体能够更为有效的诱导这类抗体的产生，这为深入研究这类新型抗体带来了契机。本课题将在这些原创发现的基础上，结合抗体组学技术、结构生物学技术、生物信息学及BCR重构技术对这类抗体的作用机理、诱导机制及相应免疫原设计进行深入的研究，为设计出能够诱导这类具有原位崩解作用的新型高效中和抗体的疫苗提供理论基础。

The invention and use of vaccines is one of the most outstanding achievements in the history of human medicine. Vaccines induced effective neutralizing antibody response, especially in viral infectious diseases, has been the most effective means to prevent viral infection. In the previous study on hepatitis E virus, our team found a new class of neutralizing antibodies. Unlike classical neutralizing antibodies, these new antibodies can induce in-situ disintegration and direct inactivation of the virus without the involvement of other immune system members. The discovery of such antibodies and their epitopes will provide new ideas for vaccine research for some pathogens (such as influenza virus and HIV) that are highly mutated in classical antibody epitopes or have difficulty in inducing a stable antibody response. However, the mechanism of neutralizing and induction of these antibodies is still unknown. In our further study, we also found that some recombinant particle-antigens can induce the production of such antibodies more effectively than natural pathogens, which provides an opportunity for further study of such new antibodies. On the basis of these original findings, this project will combine antibody omics, structural biology, bioinformatics methods and BCR reconstruction technology to conduct in-depth research on the mechanism of neutralizing, induction and corresponding immunogen design of such antibodies, providing a theoretical basis for the design of a new type of efficient-neutralizing-antibody-inducing vaccine.