Harro Janette M, Peters Brian M, O'May Graeme A, Archer Nathan, Kerns Patrick, Prabhakara Ranjani, Shirtliff Mark E
Department of Microbial Pathogenesis, Dental School, University of Maryland, Baltimore, MD, USA.
FEMS Immunol Med Microbiol. 2010 Aug;59(3):306-23. doi: 10.1111/j.1574-695X.2010.00708.x. Epub 2010 May 29.
Vaccine development against pathogenic bacteria is an imperative initiative as bacteria are gaining resistance to current antimicrobial therapies and few novel antibiotics are being developed. Candidate antigens for vaccine development can be identified by a multitude of high-throughput technologies that were accelerated by access to complete genomes. While considerable success has been achieved in vaccine development against bacterial pathogens, many species with multiple virulence factors and modes of infection have provided reasonable challenges in identifying protective antigens. In particular, vaccine candidates should be evaluated in the context of the complex disease properties, whether planktonic (e.g. sepsis and pneumonia) and/or biofilm associated (e.g. indwelling medical device infections). Because of the phenotypic differences between these modes of growth, those vaccine candidates chosen only for their efficacy in one disease state may fail against other infections. This review will summarize the history and types of bacterial vaccines and adjuvants as well as present an overview of modern antigen discovery and complications brought about by polymicrobial infections. Finally, we will also use one of the better studied microbial species that uses differential, multifactorial protein profiles to mediate an array of diseases, Staphylococcus aureus, to outline some of the more recently identified problematic issues in vaccine development in this biofilm-forming species.
鉴于细菌对当前抗菌疗法产生耐药性且新型抗生素研发较少,针对病原菌的疫苗开发是一项势在必行的举措。通过借助完整基因组而加速发展的多种高通量技术,能够识别出用于疫苗开发的候选抗原。尽管在针对细菌病原体的疫苗开发方面已取得相当大的成功,但许多具有多种毒力因子和感染方式的菌种,在识别保护性抗原方面带来了不小的挑战。特别是,候选疫苗应结合复杂的疾病特性进行评估,无论这些疾病是浮游菌引起的(如败血症和肺炎),还是与生物膜相关的(如植入式医疗器械感染)。由于这些生长方式之间存在表型差异,仅因其在一种疾病状态下的疗效而选择的候选疫苗,可能对其他感染无效。本综述将总结细菌疫苗和佐剂的历史及类型,并概述现代抗原发现以及由多种微生物感染引发的并发症。最后,我们还将以研究较为深入的一种利用不同的多因素蛋白质谱介导一系列疾病的微生物——金黄色葡萄球菌为例,概述这种形成生物膜的菌种在疫苗开发中一些最近发现的问题。