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目的研制一种安全、有效且易于生产的热灭活肺炎链球菌死菌疫苗D39X,评价其作为肺炎链球菌候选疫苗的可行性。方法通过热灭活肺炎链球菌突变菌株D39X,得到无毒的死菌疫苗,鼻腔免疫Balb/c小鼠,每周1次,连续4周。末次免疫1周后,间接ELISA检测免疫小鼠特异性抗体水平;同时检测抗体亚型及细胞因子水平,并进行不同菌株攻毒的主动保护实验。结果免疫组小鼠血清中特异性IgG和唾液中特异性IgA显著升高,IgG亚型主要为IgG1和IgG2b;免疫小鼠脾细胞特异性分泌IL-4和IL-17A;19F型肺炎链球菌在免疫小鼠中的载量显著低于对照组小鼠;灭活D39X黏膜免疫可有效延长肺炎链球菌D39、6B型和3型感染小鼠的生存时间;被动免疫也具有保护作用。结论热灭活的D39X黏膜免疫可诱导小鼠产生体液免疫和细胞免疫反应,有效抵抗不同血清型肺炎链球菌的感染,是一种有开发前景的肺炎链球菌疫苗。
Objective To develop a safe, effective and easy-to-produce heat-killed S. pneumoniae dead-cell vaccine D39X and evaluate its feasibility as a candidate pneumococcal vaccine. Methods The non-toxic dead bacterium vaccine was obtained by heat inactivation of Streptococcus pneumoniae mutant strain D39X. Balb / c mice were immunized nasally once a week for 4 weeks. One week after the last immunization, the level of specific antibody in the immunized mice was detected by indirect ELISA. At the same time, the antibody subtypes and cytokines levels were detected, and the active protection experiments of different strains were carried out. Results The specific IgA of specific IgG and saliva in the serum of immunized mice were significantly increased. The IgG subtypes were mainly IgG1 and IgG2b. The splenocytes of immunized mice secreted IL-4 and IL-17A specifically. The immune load of mice was significantly lower than that of the control mice. Inactivation of D39X mucosal immunity could prolong the survival time of S. pneumoniae D39, 6B and 3 infected mice. Passive immunization also had protective effect. Conclusions Heat-inactivated D39X mucosal immunization can induce humoral and cellular immune response in mice and effectively resist the infection of different serotypes of S. pneumoniae. Therefore, it is a promising pneumococcal vaccine.