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Identification and characterization of antigens as vaccine candidates against Klebsiella pneumoniae

机译:鉴定和表征作为针对肺炎克雷伯菌的候选疫苗的抗原

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摘要

Nosocomial infections, also called “hospital acquired infections,” occur worldwide and affect both developed and resource-poor countries, thus having a major impact on their health care systems. Klebsiella pneumoniae, which is an opportunistic Gram-negative pathogen, is responsible for causing pneumonia, urinary tract infections and septicemia in immune compromised hosts such as neonates. Unfortunately, there is no vaccine or mAb available for prophylactic or therapeutic use against K. pneumoniae infections. For this reason, we sought for a protein-based subunit vaccine capable of combating K. pneumoniae infections, by applying our ANTIGENome technology for the identification of potential vaccine candidates, focusing on conserved protein antigens present in strains with different serotypes. We identified numerous novel immunogenic proteins using genomic surface display libraries and human serum antibodies from donors exposed to or infected by K. pneumoniae. Vaccine candidate antigens were finally selected based on animal protection in a murine lethal-sepsis model. The protective and highly conserved antigens identified in this study are promising candidates for the development of a protein-based vaccine to prevent infection by K. pneumoniae.
机译:医院感染,也称为“医院获得性感染”,在世界范围内发生,并影响发达国家和资源匮乏的国家,因此对其医疗体系产生重大影响。克雷伯氏肺炎克雷伯菌是机会性革兰氏阴性病原体,可导致免疫受损的宿主(如新生儿)引起肺炎,尿路感染和败血病。不幸的是,目前尚无可用于预防或治疗肺炎克雷伯菌感染的疫苗或mAb。因此,我们通过应用我们的ANTIGENome技术来鉴定潜在的候选疫苗,重点研究存在于不同血清型菌株中的保守蛋白抗原,从而寻求一种能够抵抗肺炎克雷伯菌感染的基于蛋白质的亚单位疫苗。我们使用基因组表面展示库和来自暴露于肺炎克雷伯氏菌或感染了肺炎克雷伯氏菌的供体的人类血清抗体,鉴定了许多新颖的免疫原性蛋白质。最后基于鼠致死性败血症模型中的动物保护来选择疫苗候选抗原。在这项研究中确定的保护性和高度保守的抗原是开发基于蛋白的疫苗以预防肺炎克雷伯菌感染的有希望的候选者。

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