Brucellosis vaccines: assessment of Brucella melitensis lipopolysaccharide rough mutants defective in core and O-polysaccharide synthesis and export.
Brucellosis vaccines: assessment of Brucella melitensis lipopolysaccharide rough mutants defective in core and O-polysaccharide synthesis and export.
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DOI：
10.1371/journal.pone.0002760
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发表时间：
2008-07-23
期刊：
影响因子：
3.7
通讯作者：
Moriyón I
中科院分区：
文献类型：
--
作者：
González D;Grilló MJ;De Miguel MJ;Ali T;Arce-Gorvel V;Delrue RM;Conde-Alvarez R;Muñoz P;López-Goñi I;Iriarte M;Marín CM;Weintraub A;Widmalm G;Zygmunt M;Letesson JJ;Gorvel JP;Blasco JM;Moriyón I
布鲁氏菌是引起布鲁氏菌病的兼性胞内细菌，布鲁氏菌病是被忽视的主要人畜共患病之一。在流行地区，接种疫苗是控制这种疾病的唯一有效方法。羊种布氏杆菌Rev 1是一种有效对抗由B引起的绵羊和山羊布氏杆菌病的疫苗。梅利腾氏病是人类最常见的感染源。然而，Rev 1携带一种光滑的脂多糖和一种O-多糖，该多糖可激发干扰血清学诊断的抗体，这是根除运动中的一个主要问题。正因为如此，缺乏0-多糖的粗糙布鲁氏菌突变体已被提议作为疫苗。为了检验粗疫苗的可能性，我们筛选了B。melitensis的脂多糖基因，并获得了突变体代表所有主要粗糙表型的核心寡糖和O-多糖的合成和输出。利用小鼠模型，根据突变体在不同剂量下在脾脏中的增殖和持久性，将突变体分为四种衰减模式。在巨噬细胞中，属于这些衰减模式中的三种的突变体达到布鲁氏菌特征性细胞内生态位并在细胞内繁殖，这表明它们可能是合适的疫苗候选物。毒力模式，细胞内的行为和脂多糖缺陷大致相关的保护程度的突变体后，腹膜内接种小鼠。然而，当通过皮下途径接种疫苗时，只有两种突变体与Rev 1获得的保护相匹配，尽管剂量比该参比疫苗高1000倍。这些突变体，这是封闭的O-多糖出口和积累内部O-多糖，刺激弱抗光滑脂多糖抗体。结果表明，在实验室模型中没有粗糙突变体等于Rev 1，并质疑粗糙疫苗适用于流行地区布鲁氏菌病控制的概念。
The brucellae are facultative intracellular bacteria that cause brucellosis, one of the major neglected zoonoses. In endemic areas, vaccination is the only effective way to control this disease. Brucella melitensis Rev 1 is a vaccine effective against the brucellosis of sheep and goat caused by B. melitensis, the commonest source of human infection. However, Rev 1 carries a smooth lipopolysaccharide with an O-polysaccharide that elicits antibodies interfering in serodiagnosis, a major problem in eradication campaigns. Because of this, rough Brucella mutants lacking the O-polysaccharide have been proposed as vaccines. To examine the possibilities of rough vaccines, we screened B. melitensis for lipopolysaccharide genes and obtained mutants representing all main rough phenotypes with regard to core oligosaccharide and O-polysaccharide synthesis and export. Using the mouse model, mutants were classified into four attenuation patterns according to their multiplication and persistence in spleens at different doses. In macrophages, mutants belonging to three of these attenuation patterns reached the Brucella characteristic intracellular niche and multiplied intracellularly, suggesting that they could be suitable vaccine candidates. Virulence patterns, intracellular behavior and lipopolysaccharide defects roughly correlated with the degree of protection afforded by the mutants upon intraperitoneal vaccination of mice. However, when vaccination was applied by the subcutaneous route, only two mutants matched the protection obtained with Rev 1 albeit at doses one thousand fold higher than this reference vaccine. These mutants, which were blocked in O-polysaccharide export and accumulated internal O-polysaccharides, stimulated weak anti-smooth lipopolysaccharide antibodies. The results demonstrate that no rough mutant is equal to Rev 1 in laboratory models and question the notion that rough vaccines are suitable for the control of brucellosis in endemic areas.
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影响因子：
3.1
作者：
Allen, CA;Adams, LG;Ficht, TA
通讯作者：
Ficht, TA
影响因子：
3.1
作者：
CAROFF, M;BUNDLE, DR;DUNCAN, JR
通讯作者：
DUNCAN, JR
DOI：
10.1084/jem.20030088
发表时间：
2003-08-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Celli J;de Chastellier C;Franchini DM;Pizarro-Cerda J;Moreno E;Gorvel JP
通讯作者：
Gorvel JP
影响因子：
3.2
作者：
Aragon, V;Diaz, R;Moriyon, I
通讯作者：
Moriyon, I
影响因子：
6.4
作者：
FREEMAN, BA;CIRCO, R;KROSS, DJ
通讯作者：
KROSS, DJ