Epitope-based vaccination against pneumonic tularemia

被引:36
|
作者
Gregory, Stephen H. [1 ,2 ]
Mott, Stephanie [2 ]
Phung, Jennifer [2 ]
Lee, Jinhee [3 ]
Moise, Leonard [4 ,5 ]
McMurry, Julie A. [4 ]
Martin, William [4 ]
De Groot, Anne S. [4 ,5 ]
机构
[1] Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA
[2] Brown Univ, Warren Alpert Med Sch, Providence, RI 02903 USA
[3] Univ Massachusetts, Sch Med, Worcester, MA USA
[4] EpiVax Inc, Providence, RI USA
[5] Univ Rhode Isl, Inst Immunol & Informat, Providence, RI 02908 USA
基金
美国国家卫生研究院;
关键词
Francisella tularensis; Lungs; DNA vaccine; FRANCISELLA-TULARENSIS LVS; TUMOR-NECROSIS-FACTOR; VIRULENT TYPE-A; PROTECTIVE IMMUNITY; INTRANASAL VACCINATION; RESPIRATORY-INFECTION; AEROSOL CHALLENGE; INTERFERON-GAMMA; FACTOR-ALPHA; STRAINS;
D O I
10.1016/j.vaccine.2009.06.101
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:5299 / 5306
页数:8
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