Fattom A I, Sarwar J, Ortiz A, Naso R
W.W. Karakawa Microbial Pathogenesis Laboratory, NABI, Rockville, Maryland 20852, USA.
Infect Immun. 1996 May;64(5):1659-65. doi: 10.1128/iai.64.5.1659-1665.1996.
The efficacy of capsular polysaccharide (CP)-specific antibodies elicited by active immunization with vaccines composed of Staphylococcus aureus types 5 and 8 CP linked to Pseudomonas aeruginosa exoprotein A or with immune immunoglobulin G (I-IgG) obtained from vaccinated plasma donors was tested in lethal and sublethal bacterial mouse challenge models. A dose of 2 x 10(5) CFU of S. aureus type 5 CP per mouse administered intraperitoneally (i.p.) with 5% hog mucin was found to cause 80 to 100% mortality in BALB/c mice within 2 to 5 days. Mice passively immunized i.p. 24 h earlier or subcutaneously 48 h earlier with 0.5 ml of I-IgG showed significantly higher average survival rates than animals receiving standard IgG or saline (P < 0.01) following the bacterial challenge. Animals actively immunized with the monovalent type 5 CP-P. aeruginosa exoprotein A conjugate showed a survival rate of 73% compared with 13% in phosphate-buffered saline-immunized animals. The prechallenge geometric mean titer of type 5 CP antibodies in animals that died was significantly (P < 0.05) lower than that of animals which survived the challenge (95.7 versus 223.6 micrograms/ml, respectively). The IgG was further evaluated in mice challenged i.p. with a sublethal dose of 5 x 10(4) CFU per mouse. Serial blood counts were performed on surviving animals at 6, 12, 24, and 48 h. Surviving animals were sacrificed at 72 h, and bacterial counts were performed on their kidneys, livers, and peritoneal lavage fluids. Animals receiving I-IgG had lower bacterial counts in blood samples and lower bacterial densities in kidneys, livers, and peritoneal lavage samples than mice immunized with standard IgG (P < 0.05). These data suggest that S. aureus type 5 CP antibodies induced by active immunization or administered by passive immunization confer protection against S. aureus infections.
在致死性和亚致死性细菌小鼠攻击模型中,测试了用与铜绿假单胞菌外毒素A连接的5型和8型金黄色葡萄球菌荚膜多糖(CP)组成的疫苗进行主动免疫所引发的CP特异性抗体,或从接种疫苗的血浆供体获得的免疫免疫球蛋白G(I-IgG)的功效。发现每只小鼠腹腔注射(i.p.)2×10⁵CFU的5型金黄色葡萄球菌CP并加入5%猪粘蛋白,会在2至5天内导致BALB/c小鼠80%至100%的死亡率。在细菌攻击后,提前24小时腹腔注射或提前48小时皮下注射0.5 ml I-IgG进行被动免疫的小鼠,其平均存活率显著高于接受标准IgG或生理盐水的动物(P<0.01)。用单价5型CP-铜绿假单胞菌外毒素A偶联物进行主动免疫的动物存活率为73%,而用磷酸盐缓冲盐水免疫的动物存活率为l3%。死亡动物体内5型CP抗体攻击前的几何平均滴度显著低于(P<0.05)在攻击中存活的动物(分别为95.7与223.6微克/毫升)。进一步在每只小鼠腹腔注射亚致死剂量5×10⁴CFU的小鼠中评估IgG。在6、12、24和48小时对存活动物进行连续血细胞计数。在72小时处死存活动物,并对其肾脏、肝脏和腹腔灌洗液进行细菌计数。接受I-IgG的动物血液样本中的细菌计数以及肾脏、肝脏和腹腔灌洗样本中的细菌密度低于用标准IgG免疫的小鼠(P<0.05)。这些数据表明,主动免疫诱导或被动免疫给予的5型金黄色葡萄球菌CP抗体可提供针对金黄色葡萄球菌感染的保护。