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目的研制一种安全、有效且易于生产的肺炎链球菌疫苗,探讨其在BALB/c小鼠中的有效性。方法通过热灭活肺炎链球菌标准菌株D39,得到无毒的、失去感染致病的能力的HID39,用HID39作为疫苗对随机分为阴性对照组(NC)、皮下免疫组(SC)和鼻内免疫组(IN)的小鼠进行免疫,ELISA法检测各组小鼠血清和唾液中的抗体及抗体亚型,并用不同菌株攻毒来评价HID39疫苗的效果。结果 HID39免疫小鼠后,SC组血清中IgG效价高达(12 800±8744),IN组的效价为(4032±1652),而SC组唾液中未检测到IgA,IN组却有(400±197)。抗体亚型以IgG1,IgG2a,IgG2b为主,未检测到IgG3。TIGR4在小鼠鼻内、肺和脑的定植显著下降,其中鼻内免疫的定植量最少。HID39鼻内免疫和皮下免疫都可显著提高致死剂量肺炎链球菌D39、血清型3和6B型感染小鼠的生存率,其中鼻内免疫的小鼠生存率均可达50%,抗血清的被动保护的生存率在50%以上。结论 HID39是一种较成功的肺炎链球菌疫苗,用它免疫小鼠可抵抗肺炎链球菌的感染。
Objective To develop a safe, effective and easy-to-produce S. pneumoniae vaccine and explore its effectiveness in BALB / c mice. Methods HID39 was obtained by heat inactivation of Streptococcus pneumoniae standard strain D39. The HID39 strain was divided into negative control group (NC), subcutaneous immunized group (SC) and intranasal Immunized group (IN) mice were immunized. The antibody and antibody subtypes in serum and saliva of each group were detected by ELISA, and the effect of HID39 vaccine was evaluated by challenge with different strains. Results After immunization with HID39, the serum IgG titer in SC group was as high as (12 800 ± 8744), that in IN group was (4032 ± 1652), while no IgA was detected in saliva of SC group (400 ± 197). Antibody subtype IgG1, IgG2a, IgG2b dominated, did not detect IgG3. TIGR4 in mice nose, lung and brain colonization decreased significantly, of which intranasal immune colonization at least. HID39 intranasal immunization and subcutaneous immunization can significantly increase the lethal dose of Streptococcus pneumoniae D39, serotypes 3 and 6B infection in mice survival rate, which intranasally immunized mice survival rates were up to 50%, antiserum passive The survival rate of protection is above 50%. Conclusion HID39 is a more successful S. pneumoniae vaccine that can be used to immunize mice against Streptococcus pneumoniae infection.