Immunization with a Combination of Three Pneumococcal Proteins Confers Additive and Broad Protection against Streptococcus pneumoniae Infections in Mice
Immunization with a Combination of Three Pneumococcal Proteins Confers Additive and Broad Protection against Streptococcus pneumoniae Infections in Mice
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DOI：
10.1128/iai.00473-09
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发表时间：
2010-03-01
影响因子：
3.1
通讯作者：
Yin, Yibing
中科院分区：
文献类型：
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作者：
Wu, Kaifeng;Zhang, Xuemei;Yin, Yibing
基于肺炎球菌多糖的疫苗在预防肺炎球菌感染方面是有效的;然而，一些缺点阻碍了它们在发展中国家和不发达国家的广泛使用。在此，我们评估了ATP依赖性酪蛋白溶解蛋白酶（ClpP）、肺炎球菌溶血素突变体（Δ A146 Ply）、推定的硫辛酸-蛋白连接酶（Lpl）或其组合对小鼠中肺炎球菌感染的保护作用。用不同的肺炎球菌菌株腹膜内和/或鼻内攻击接种疫苗的小鼠。在用肺炎球菌菌株D39（血清型2）的腹膜内攻击模型中，用三种抗原的组合获得了最显著的保护。类似地，对于鼻内激发模型，（i）对于三种抗原的组合，观察到肺中细菌的相加清除，和（ii）组合疫苗赋予针对四种最常见的肺炎球菌菌株中的三种（血清型14、19 F和23 F）的鼻内感染的完全保护和对肺炎球菌菌株6 B的80%保护。即便如此，对这种组合的免疫力可以保护免受四种血清型混合的肺炎球菌感染。我们的结果表明，该组合疫苗与目前使用的疫苗（PCV 7和PPV 23）一样有效。这些结果表明，肺炎球菌抗原的组合的系统免疫可以提供针对肺炎链球菌在肺炎和脓毒症感染模型的累加和广泛的保护。
Pneumococcal polysaccharide-based vaccines are effective in preventing pneumococcus infection; however, some drawbacks preclude their widespread use in developing and undeveloped countries. Here, we evaluated the protective effects of ATP-dependent caseinolytic protease (ClpP), pneumolysin mutant (Delta A146 Ply), putative lipoate-protein ligase (Lpl), or combinations thereof against pneumococcal infections in mice. Vaccinated mice were intraperitoneally and/or intranasally challenged with different pneumococcal strains. In intraperitoneal challenge models with pneumococcal strain D39 (serotype 2), the most striking protection was obtained with the combination of the three antigens. Similarly, with the intranasal challenge models, (i) additive clearance of bacteria in lungs was observed for the combination of the three antigens and (ii) a combination vaccine conferred complete protection against intranasal infections of three of the four most common pneumococcal strains (serotypes 14, 19F, and 23F) and 80% protection for pneumococcal strain 6B. Even so, immunity to this combination could confer protection against pneumococcal infection with a mixture of four serotypes. Our results showed that the combination vaccine was as effective as the currently used vaccines (PCV7 and PPV23). These results indicate that system immunization with the combination of pneumococcal antigens could provide an additive and broad protection against Streptococcus pneumoniae in pneumonia and sepsis infection models.