A Staphylococcus aureus capsular polysaccharide (CP) vaccine and CP-specific antibodies protect mice against bacterial challenge

A Staphylococcus aureus capsular polysaccharide (CP) vaccine and CP-specific antibodies protect mice against bacterial challenge
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DOI:
10.1128/iai.64.5.1659-1665.1996
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发表时间:
1996-05-01
影响因子:
3.1
通讯作者:
Naso, R
Naso, R
中科院分区:
医学2区
文献类型:
--
作者:
Fattom, AI;Sarwar, J;Naso, R

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在致死和亚致死细菌小鼠攻击模型中,测试了由与铜绿假单胞菌外蛋白 A 连接的金黄色葡萄球菌 5 型和 8 型 CP 组成的疫苗或从接种的血浆供体获得的免疫球蛋白 G (I-IgG) 主动免疫所引发的荚膜多糖 (CP) 特异性抗体的功效。研究发现,每只小鼠腹腔注射 2 x 10(5) CFU 的金黄色葡萄球菌 5 型 CP 和 5% 猪粘蛋白,可在 2 至 5 天内导致 BALB/c 小鼠死亡 80% 至 100%。小鼠腹膜内被动免疫提前 24 小时或提前 48 小时皮下注射 0.5 ml I-IgG 的平均存活率明显高于细菌攻击后接受标准 IgG 或盐水的动物 (P < 0.01)。使用单价 5 型 CP-P 主动免疫动物。铜绿假单胞菌外蛋白 A 缀合物的存活率为 73%,而磷酸盐缓冲盐水免疫动物的存活率为 13%。死亡动物中5型CP抗体的攻击前几何平均滴度显着(P<0.05)低于攻击中幸存的动物(分别为95.7μg/ml和223.6μg/ml)。在腹膜内攻击的小鼠中进一步评估了 IgG。每只小鼠的亚致死剂量为 5 x 10(4) CFU。在 6、12、24 和 48 小时对存活的动物进行连续血细胞计数。 72小时处死存活的动物,并对它们的肾脏、肝脏和腹膜灌洗液进行细菌计数。与标准 Ige 免疫的小鼠相比,接受 I-IgG 免疫的动物血液样本中的细菌计数较低,肾脏、肝脏和腹腔灌洗样本中的细菌密度也较低(P < 0.05)。这些数据表明,通过主动免疫诱导或通过被动免疫施用的金黄色葡萄球菌5型CP抗体赋予针对金黄色葡萄球菌感染的保护。
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 mu g/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 Ige (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.