Multivalent DNA vaccine protects mice against pulmonary infection caused by Pseudomonas aeruginosa

Multivalent DNA vaccine protects mice against pulmonary infection caused by Pseudomonas aeruginosa
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DOI:
10.1016/j.vaccine.2006.05.077
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发表时间:
2006-09-11
期刊:
影响因子:
5.5
通讯作者:
Okuda, Kenji
Okuda, Kenji
中科院分区:
医学3区
文献类型:
--
作者:
Saha, Sukumar;Takeshita, Fumihiko;Okuda, Kenji

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为研制有效的铜绿假单胞菌疫苗,对多价DNA疫苗的免疫原性进行了评价。分别以外膜蛋白融合蛋白(OprF/OprI)、蛋白调节III型分泌系统(PcrV)或附件(PIIA)为靶点的3种不同载体,通过肌肉电穿孔(ImEPT)或基因枪免疫小鼠。经imEPT免疫的多价DNA疫苗对致死性肺炎的保护力最强。免疫保护作用最强的是血清Th1为主的多价免疫球蛋白、肺泡巨噬细胞炎症蛋白2(MIP-2)和干扰素-γ的水平,以及鼻腔攻击后肺泡灌洗液中中性粒细胞和巨噬细胞的数量。这些结果提示铜绿假单胞菌多价DNA疫苗有可能在临床应用。(C)2006爱思唯尔有限公司。保留所有权利。
For efficacious vaccine development against Pseudomonas aeruginosa (P aeruginosa), the immunogenicity of multivalent DNA vaccine was evaluated. Three different plasmids each targeting a fusion of outer membrane proteins (OprF/OprI), a protein regulating type III secretion system (PcrV), or an appendage (PiIA) were prepared and mice were immunized with single (monovalent) or a combination of these plasmids (multivalent) via intramuscular electroporation (imEPT) or gene gun. Immunization with multivalent DNA vaccine via imEPT induced the most potent protection against lethal pneumonia. Although the serum levels of IgG binding to whole bacteria cells were comparable between groups, the strongest immune protection was associated with the serum levels of Th1-dominated multivalent IgG, the bronchoalveolar levels of macrophage inflammatory protein 2 (MIP-2) and IFN-gamma, and the number of neutrophils and macrophages in the bronchoalveolar lavage following intranasal challenge. These results implied the possible clinical application of multivalent DNA vaccine against P. aeruginosa. (c) 2006 Elsevier Ltd. All rights reserved.