金黄色葡萄球菌四组分候选疫苗的免疫原性和保护效力评价

Immunogenicity and protective efficacy of four-component candidate vaccine against Staphylococcus aureus

目的评价金黄色葡萄球菌四组分候选疫苗(Staphylococcus aureus 4-antigen vaccine,SA4Ag)的免疫原性及保护效力。方法用荚膜多糖5型(capsular polysaccharide type 5,CP5)结合物、CP8结合物、重组蛋白突变无毒α-溶血素(mutant nontoxicα-hemolysin,mHla)、锰转运蛋白C(manganese transporter C,MntC)配制成SA4Ag。用SA4Ag免疫小鼠,同时设铝佐剂对照组,ELISA法检测小鼠血清中特异性IgG各亚型抗体效价。另取小鼠免疫SA4Ag后,分别注射亚致死剂量金黄色葡球菌(简称金葡菌)国际标准株49521(CP5型)和49525(CP8型)菌液,检测血液、心脏及肾脏中细菌载量;检查心脏、肾脏的病理改变;观察小鼠生存状态及体重变化。另取小鼠免疫SA4Ag后,分别注射致死剂量金葡菌国际标准株49521、49525及6株临床分离株(WLMQ-1801、LZ-3211、NN-567、NN-591、SY-1490、HF-1588)菌液,观察小鼠存活情况。结果小鼠免疫SA4Ag后可诱导产生各抗原组分的特异性IgG1、IgG2a和IgG2b亚型抗体,IgG1水平均明显高于IgG2a(P<0.001)。与对照组比较,感染亚致死剂量金葡菌国际标准株49521和49525菌液后,免疫组小鼠血液、心脏、肾脏中细菌载量明显降低(P<0.05);心、肾组织病理损伤和炎性细胞浸润减轻;可维持较好的生存状态,体重下降幅度明显减小(P<0.05)。与对照组比较,感染致死剂量金葡菌国际标准株49521、49525及6株临床分离株后,免疫组小鼠生存率提高了70%~90%(P<0.05)。结论SA4Ag具有较好的免疫原性,在小鼠全身感染模型中具有较好的保护效力。

Objective To evaluate the immunogenicity and protective efficacy of four-component candidate vaccine against Staphylococcus aureus,also known as Staphylococcus aureus 4-antigen vaccine(SA4Ag).Methods SA4Ag was prepared with capsular polysaccharide type 5(CP5)conjugate,CP8 conjugate,recombinant mutant nontoxicα-hemolysin(mH1a)and manganese transporter C(MntC),with which mice were immunized,using aluminum adjuvant as control,and determined for the titers of specific IgG antibodies of various subtypes by ELISA.Another mice were immunized by SA4Ag and challenged with sublethal doses of international standard strains 49521(type CP5)and 49525(type CP8)of S.aureus respectively,of which the bacterial loads in blood,heart and kidney were determined,while the pathological changes of heart and kidney were examined,and the survival status and body weight were observed.Meanwhile,another mice were immunized with SA4Ag and challenged with lethal doses of strains 49521,49525 and six clinical isolates(WLMQ-1801,LZ-3211,NN-567,NN-591,SY-1490 and HF-1588)respectively,and observed for survival.Results Specific antibodies of subtypes IgG1,IgG2a and IgG2b were induced in mice by SA4Ag,while the IgG1 level was higher than IgG2a level(P<0.001).Compared with those in control group,the bacterial loads in blood,heart and kidney of immunized mice decreased significantly after challenge with sublethal doses of strains 49521 and 49525(P<0.05),while the pathological damage and inflammatory cell infiltration in heart and kidney tissues were relieved,the survival status was improved,and the weight loss decreased(P<0.05).However,compared with that in control group,the survival rate of immunized mice increased by 70%~90%after challenge with lethal doses of strains 49521,49525 and six clinical isolates(P<0.05).Conclusion SA4Ag showed good immunogenicity and good protective efficacy in mouse model of systemic infection.