Lundberg Urban, Senn Beatrice M, Schüler Wolfgang, Meinke Andreas, Hanner Markus
Intercell AG, Campus Vienna Biocenter 3; Vienna, Austria.
Hum Vaccin Immunother. 2013 Mar;9(3):497-505. doi: 10.4161/hv.23225. Epub 2012 Dec 18.
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.
医院感染,也称为“医院获得性感染”,在全球范围内均有发生,对发达国家和资源匮乏国家都会产生影响,因此对其医疗保健系统造成重大冲击。肺炎克雷伯菌是一种机会性革兰氏阴性病原体,可导致新生儿等免疫功能低下宿主发生肺炎、尿路感染和败血症。不幸的是,目前尚无用于预防或治疗肺炎克雷伯菌感染的疫苗或单克隆抗体。因此,我们通过应用我们的抗原组技术来鉴定潜在的疫苗候选物,寻找一种能够对抗肺炎克雷伯菌感染的基于蛋白质的亚单位疫苗,重点关注不同血清型菌株中存在的保守蛋白质抗原。我们使用基因组表面展示文库和来自接触过或感染过肺炎克雷伯菌的供体的人血清抗体,鉴定了许多新型免疫原性蛋白质。最终根据小鼠致死性败血症模型中的动物保护情况选择疫苗候选抗原。本研究中鉴定出的具有保护作用且高度保守的抗原是开发基于蛋白质的疫苗以预防肺炎克雷伯菌感染的有前景的候选物。