【摘要】 目的评价空肠弯曲菌多价DNA疫苗对周围神经的免疫安全性和保护性。方法以空肠弯曲菌HS:19全菌抗原免疫为阳性对照组,将不同效价的空肠弯曲菌DNA疫苗滴鼻免疫BALB/c小鼠,采用ELISA法检测免疫后小鼠血清抗GM1抗体水平;采用组织病理学检查观察免疫后小鼠坐骨神经组织结构改变。将上述小鼠免疫后4周的血清注射于健康BALB/c小鼠坐骨神经外膜下,4周后观察被注射坐骨神经组织病理学改变;在此基础上,采用空肠弯曲菌HS:19重复攻击方式进行灌胃攻击,以对该疫苗的免疫保护作用进行评价。结果空肠弯曲菌HS:19全菌抗原经鼻免疫小鼠后诱发了周围神经显著的免疫性损伤,坐骨神经原纤维病变发生率高达66.3%,主要表现为广泛的轴索变性,同时伴有血清抗GM1抗体增高,末次免疫后第4周其P/N值达8.13;将免疫后的小鼠血清注射于健康小鼠坐骨神经外膜下后发生了更加严重的免疫性损伤。而空肠弯曲菌多价DNA疫苗却不能诱导血清抗GM1抗体增高,以其免疫后的血清行神经外膜下注射亦无明显周围神经免疫性损伤发生;另外,其诱导的特异性免疫应答可有效保护小鼠免遭空肠弯曲菌感染,显著降低被攻击小鼠周围神经组织病变的发生率。结论空肠弯曲菌多价DNA疫苗对周围神经具有安全无毒性和免疫保护作用。更多还原

【Abstract】 Objective To evaluate the immune protective efficacy and safety of polyvalent DNA vaccines against C.jejuni to peripheral nerves.Methods BALB/c mice were immunized with various C.jejuni DNA vaccines and whole antigens of C.jejuni HS:19 intranasally.ELISA assay was carried to detect serumal anti-ganglioside GM1 antibodies at weeks 2,4,6,8 after the last immunization.Mice were sacrificed and sciatic nerves were taken for histopathologic study at the 8th week after the last immunization.Meanwhile at the 4th week after the last immunization,sera of the mice immunized with various C.jejuni DNA vaccines and whole antigens of C.jejuni HS:19 were collected and injected subperineurially into sciatic nerves of healthy BALB/c mice respectively.At the 4th week after injection,histopathologic study of sciatic nerves was performed.On the basis of the above experiments,mice were attacked repeatedly with intragastric administration of C.jejuni HS:19 at the 8th week after the last immunization and the histopathology of mice peripheral nerves was investigated after these attacks.Results As positive control,inactivated whole antigens of C.jejuni HS:19 showed obvious immuno-damage of peripheral nerves with the incidence of pathologic abnormalities of teased fibers up to 66.3% and axonal degeneration was the predominant abnormality.Meanwhile there was increased serum level of anti-GM1 antibodies with P/N went up to 8.13.After immunized serum subperineurial injection,the incidence of abnormal teased fibers from the mice accepted sera from mice immunized with whole antigens of C.jejuni HS:19 was 100.0%.But in polyvalent DNA vaccines group no anti-GM1 antibodies and sciatic nerves damages were found in the imunized mice,as well as they could effectively resist C.jejuni infection and prevent the mice from damage of peripheral nerves.Conclusions The polyvalent DNA vaccine against C jejuni was safe for the experimental animals even in those been attacked repeatedly by C jejuni HS:19 and showed protective efficacy to peripheral nerves.更多还原