不同电荷壳寡糖衍生物的新型疫苗佐剂活性及其免疫调节机理研究

Chitosan oligosaccharide is the only positive-charged bioactive oligosaccharide in nature. Previous studies showed chitosan oligosaccharide effectively activated both cellular immunity and humoral immunity, which suggested its potential application as a vaccine adjuvant. Charge level of chitosan oligosaccharide derivatives influences some of their bioactivities, however, whether charge level affects their immune adjuvant activity remains to be investigated. In this project, chitosan oligosaccharides with different charge levels combined with the inactivated porcine reproductive and respiratory syndrome (PRRS) vaccine and hepatitis b subunit vaccine (HBsAg) will be used for animal immunization, respectively. After that, the antibody titer and antibody subtype will be analyzed to evaluate the immune-enhancing effects of such potential oligosaccharide adjuvants on the cellular immunity and humoral immunity. Also, both in vitro and in vivo immunological mechanisms will be explored. Based on studies above, the relationship between the charge level and the adjuvant activity will be elucidated. Our studies will not gain insight into the molecular mechanism of immune regulation of such oligosaccharide adjuvants, but lay a solid foundation for the development of new vaccine adjuvants. In addition, this project aims to provide theoretical basis for the finding of safe and effective vaccines against major human or animal infectious diseases.

壳寡糖是目前发现的唯一天然带正电荷的活性寡糖。它能够有效激活机体细胞免疫及体液免疫，具有良好疫苗佐剂应用前景。有研究表明壳寡糖电荷性质影响其生物活性，但尚无其电荷水平对免疫佐剂活性影响的研究报道。本课题拟制备不同电荷壳寡糖衍生物并分别与猪蓝耳病灭活疫苗（PRRS）及人乙肝亚单位疫苗（HBsAg）联合用于动物免疫，测定免疫动物血清中的抗体滴度及抗体亚型，探讨其作为疫苗佐剂对不同抗原产生的细胞免疫和体液免疫功能的增强效应，判断其作为疫苗佐剂的活性与电荷之间的关系，在细胞和动物水平进行免疫活性机理分析，评价不同电荷壳寡糖衍生物作为疫苗佐剂的安全性，阐明电荷性质对壳寡糖免疫佐剂活性影响的分子机制，为研制具有良好生物相容性的新型兽用和人用疫苗佐剂奠定理论基础。

壳寡糖是目前发现的唯一带正电荷的活性寡糖。它能够有效激活机体细胞及体液免疫，具有良好疫苗佐剂应用前景。有研究表明壳寡糖电荷性质影响其生物活性，但尚无其电荷水平对免疫佐剂活性影响的研究报道。本课题制备了不同电荷壳寡糖衍生物并分别与猪蓝耳病灭活疫苗（PRRS）及人乙肝亚单位疫苗（HBsAg）联合用于动物免疫，测定免疫后的抗体滴度及抗体亚型，探讨其作为疫苗佐剂对不同抗原产生的细胞免疫和体液免疫功能的增强效应，判断其作为疫苗佐剂的活性与电荷之间的关系，在细胞和动物水平进行免疫活性机理分析，评价不同电荷壳寡糖及其衍生物作为疫苗佐剂的安全性，阐明电荷性质对壳寡糖免疫佐剂活性影响的分子机制，为研制具有良好生物相容性的新型兽用和人用疫苗佐剂奠定理论基础。