Epitope-based vaccination against pneumonic tularemia

Epitope-based vaccination against pneumonic tularemia
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DOI:
10.1016/j.vaccine.2009.06.101
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发表时间:
2009-08-27
期刊:
影响因子:
5.5
通讯作者:
De Groot, Anne S.
De Groot, Anne S.
中科院分区:
医学3区
文献类型:
--
作者:
Gregory, Stephen H.;Mott, Stephanie;De Groot, Anne S.

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土拉热弗朗西丝菌(Francisella tularensis)是土拉菌病的病原体,是已知的最具感染性的细菌病原体之一。目前还没有疫苗被批准用于公众使用。以前,我们确定了特异性识别的抗原表位的T细胞从个人感染土拉热菌。在这里,我们报告说,基于这些表位构建的亚单位疫苗引起保护性免疫的“人源化”HLA II类(DRB 1 *0401)转基因小鼠。用致死剂量的土拉热杆菌(活疫苗株)经皮内攻毒的接种小鼠显示促炎细胞因子产生迅速增加,肺部微生物数量减少,同时存活率增加。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细胞内细菌病原体特异性疫苗的开发。(C)2009爱思唯尔有限公司保留所有权利。
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 E 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 E 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. (C) 2009 Elsevier Ltd. All rights reserved.