目的: 探讨溶血性链球菌-流感嗜血杆菌B型-肺炎链球菌-金黄色葡萄球菌-铜绿假单胞菌-肺炎克雷伯菌联合疫苗（SHSSPK）对肺炎双球菌感染小鼠的免疫反应影响。方法: 48只小鼠被随机分为4组（12只/组）：PBS组、SHSSPK低剂量组（SHSSPK-L）、SHSSPK中剂量组（SHSSPK-M）、SHSSPK高剂量组（SHSSPK-H）。SHSSPK不同剂量组每隔2周接受1次口服SHSSPK免疫,剂量分别为0.1 mg/mL、0.2 mg/mL、0.4 mg/mL。PBS组则口服等体积PBS。在第8周,每组处死6只小鼠,然后收集脾脏和血清样本,用以检测血清抗体和细胞因子。其余6只小鼠通过呼吸道感染肺炎球菌,并评估小鼠的体液和细胞免疫反应。结果: SHSSPK-L组、SHSSPK-M组和SHSSPK-H组的血清抗体IgG和IgA的水平从第4周开始逐渐升高,明显高于PBS组。与PBS组相比,SHSSPK不同剂量组脾细胞的抗原特异性增殖反应和Th1型细胞因子IFN-γ、IL-2的水平均显著增加,以及肺部匀浆中肺炎双球菌菌落数量和肺组织病理学评分均显著降低。与PBS组相比,SHSSPK不同剂量组在肺部产生的IFN-γ和TNF-α水平明显降低,并且这种降低呈剂量依赖性。结论: SHSSPK免疫可以诱导小鼠针对肺炎双球菌的体液和细胞免疫反应,减少细菌负担,并抑制呼吸道支原体感染。
Abstract
Objective To investigate the effect of combined vaccine of Hemolytic streptococcus-Haemophilus influenzae type B-Streptococcus pneumoniae-Staphylococcus aureus-Pseudomonas aeruginosa-Klebsiella pneumoniae (SHSSPK) on the immune response of mice infected with diplococcus pneumoniae. Methods Forty-eight mice were randomly divided into four groups (12 mice per group): PBS group, SHSSSPK low dose group (SHSSSPK-L), SHSSSPK medium dose group (SHSSSPK-M), and SHSSSPK high dose groups (SHSSSPK-H). Different dose groups of SHSSSPK received oral SHSSSPK immunization once every two weeks, with doses of 0.1 mg/mL, 0.2 mg/mL and 0.4 mg/mL respectively. In PBS group, the same volume of PBS was taken orally. At the eighth week, six mice in each group were killed, and then spleen and serum samples were collected to detect serum antibodies and cytokines. The other six mice were infected with pneumococcus through respiratory tract to evaluate the humoral and cellular immune responses of mice. Results The levels of serum Ag-specific antibodies IgG and IgA in the SHSSPK-L, SHSSPK-M and SHSSPK-H groups gradually increased from week 2 and were significantly higher than those in the PBS group. The levels of antigen-specific proliferative responses and Th1-type cytokines IFN-γ and IL-2 in splenocytes were significantly increased in the SHSSPK different dose groups compared with the PBS group, as well as the number of S. pneumoniae colonies in lung homogenates and lung histopathology scores were significantly decreased. The levels of IFN-γ and TNF-α produced in the lungs were significantly lower in the different dose groups of SHSSPK compared with the PBS group, and this reduction was dose-dependent. Conclusions Immunization with SHSSPK induces humoral and cellular immune responses against S. pneumoniae, reduces bacterial burden and inhibits respiratory mycoplasma infection in mice.
关键词
系统免疫 /
联合疫苗 /
小鼠 /
呼吸道感染 /
肺炎双球菌
Key words
systemic immunization /
combined vaccine /
mice /
respiratory tract infection /
Streptococcus pneumococcus
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基金
河北省卫生健康委员会医学科研项目（20201152）
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