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评估伯克霍尔德菌双组份蛋白作为疫苗以及双组份蛋白抗体作为检测试剂的效果。

Evaluating Burkholderia pseudomallei Bip proteins as vaccines and Bip antibodies as detection agents.

作者信息

Druar Chris, Yu Fei, Barnes Jodie L, Okinaka Richard T, Chantratita Narisara, Beg Steve, Stratilo Chad W, Olive Andrew J, Soltes Glenn, Russell Michelle L, Limmathurotsakul Direk, Norton Robert E, Ni Sally X, Picking William D, Jackson Paul J, Stewart Don I H, Tsvetnitsky Vadim, Picking Wendy L, Cherwonogrodzky John W, Ketheesan Natkunam, Peacock Sharon J, Wiersma Erik J

机构信息

Cangene Corporation, Mississauga, ON, Canada.

出版信息

FEMS Immunol Med Microbiol. 2008 Jan;52(1):78-87. doi: 10.1111/j.1574-695X.2007.00345.x. Epub 2007 Nov 11.

DOI:10.1111/j.1574-695X.2007.00345.x
PMID:17995960
Abstract

Burkholderia pseudomallei is a biothreat agent and an important natural pathogen, causing melioidosis in humans and animals. A type III secretion system (TTSS-3) has been shown to be critical for virulence. Because TTSS components from other pathogens have been used successfully as diagnostic agents and as experimental vaccines, it was investigated whether this was the case for BipB, BipC and BipD, components of B. pseudomallei's TTSS-3. The sequences of BipB, BipC and BipD were found to be highly conserved among B. pseudomallei and B. mallei isolates. A collection of monoclonal antibodies (mAbs) specific for each Bip protein was obtained. Most recognized both native and denatured Bip protein. Burkholderia pseudomallei or B. mallei did not express detectable BipB or BipD under the growth conditions used. However, anti-BipD mAbs did recognize the TTSS needle structures of a Shigella strain engineered to express BipD. The authors did not find that BipB, BipC or BipD are protective antigens because vaccination of mice with any single protein did not result in protection against experimental melioidosis. Enzyme-linked immunosorbent assay (ELISA) studies showed that human melioidosis patients had antibodies to BipB and BipD. However, these ELISAs had low diagnostic accuracy in endemic regions, possibly due to previous patient exposure to B. pseudomallei.

摘要

类鼻疽伯克霍尔德菌是一种生物威胁因子和重要的自然病原体,可引起人类和动物的类鼻疽。已证明III型分泌系统(TTSS-3)对其毒力至关重要。由于来自其他病原体的TTSS组件已成功用作诊断试剂和实验疫苗,因此研究了类鼻疽伯克霍尔德菌TTSS-3的组件BipB、BipC和BipD是否也是如此。研究发现,BipB、BipC和BipD的序列在类鼻疽伯克霍尔德菌和鼻疽伯克霍尔德菌分离株中高度保守。获得了针对每种Bip蛋白的单克隆抗体(mAb)集合。大多数抗体都能识别天然和变性的Bip蛋白。在所用的生长条件下,类鼻疽伯克霍尔德菌或鼻疽伯克霍尔德菌不表达可检测到的BipB或BipD。然而,抗BipD单克隆抗体确实能识别经基因工程改造以表达BipD的志贺氏菌菌株的TTSS针状结构。作者没有发现BipB、BipC或BipD是保护性抗原,因为用任何一种单一蛋白对小鼠进行疫苗接种都不能提供针对实验性类鼻疽的保护。酶联免疫吸附测定(ELISA)研究表明,人类类鼻疽患者体内有针对BipB和BipD的抗体。然而,这些ELISA在流行地区的诊断准确性较低,可能是由于患者以前接触过类鼻疽伯克霍尔德菌。

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