Gregory Stephen H, Mott Stephanie, Phung Jennifer, Lee Jinhee, Moise Leonard, McMurry Julie A, Martin William, De Groot Anne S
Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, United States.
Vaccine. 2009 Aug 27;27(39):5299-306. doi: 10.1016/j.vaccine.2009.06.101. Epub 2009 Jul 17.
Francisella tularensis, the etiological agent of tularemia, is one of the most infectious bacterial pathogens known. No vaccine is currently approved for public use. Previously, we identified epitopes recognized specifically by T cells obtained from individuals following infection with F. tularensis. Here, we report that a subunit vaccine constructed based upon these epitopes elicited protective immunity in "humanized" HLA class II (DRB1*0401) transgenic mice. Vaccinated mice challenged intratracheally with a lethal dose of F. tularensis (Live Vaccine Strain) exhibited a rapid increase in pro-inflammatory cytokine production and diminished number of organisms in the lungs, and a concurrent increased rate of survival. These results demonstrate the efficacy of an epitope-based tularemia vaccine and suggest that such an approach might be widely applicable to the development of vaccines specific for intracellular bacterial pathogens.
土拉弗朗西斯菌是兔热病的病原体,是已知最具传染性的细菌病原体之一。目前尚无获批供公众使用的疫苗。此前,我们鉴定了感染土拉弗朗西斯菌后个体的T细胞特异性识别的表位。在此,我们报告基于这些表位构建的亚单位疫苗在“人源化”HLA II类(DRB1*0401)转基因小鼠中引发了保护性免疫。用致死剂量的土拉弗朗西斯菌(活疫苗株)经气管内攻击的接种疫苗小鼠,促炎细胞因子产生迅速增加,肺内细菌数量减少,同时存活率提高。这些结果证明了基于表位的兔热病疫苗的有效性,并表明这种方法可能广泛适用于开发针对细胞内细菌病原体的疫苗。