热灭活疫苗HID39免疫小鼠可抵抗肺炎链球菌感染

Heat-inactivated vaccine HID39 against Streptococcus pneumoniae infections in mice

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 new Streptococcus pneumoniae vaccine which is safe,effective and easy to produce.The efficacy of this vaccine will be approached in BALB/c mice.Methods HID39 was a heat-inactivated vaccine candidate origin from standard strain D39,which lost virulence but kept immunogenesis.Mice were divided into negative group,subcutaneous group and intranasal group,and were vaccinated HID39.Antibodies and subclasses were detected by ELISA.And mice were challenged with different strains to evaluate the effect of vaccine.Results After immunization with HID39,the mice had the serum IgG titers reaching 12 800±8 744 in subcutaneous group and 4 032±1 652 in intranasal group,while their saliva IgA titers reaching 400±197 in the later group but undetectable in the former group.IgG1,IgG2a and IgG2b were the main antibody subclasses and IgG3 was undetectable.The colonization of TIGR4 in the nasal,lung and brain were significantly decreased,and there were the least amount of nasal immunity.Importantly,this vaccine candidate provided efficient active protection against fetal intranasal and intraperitoneal infections with D39 strain and 2 clinical strains of serotype 6B and 3.The survival percent of intranasally immunized mice was about 50%,and the survival percent of passive protection of antibody was more than 50%.Conclusion HID39 is a successful vaccine and can induce immune response against pneumococcal infections in mice.