The Brucella melitensis M5-90 phosphoglucomutase (PGM) mutant is attenuated and confers protection against wild-type challenge in BALB/c mice
The Brucella melitensis M5-90 phosphoglucomutase (PGM) mutant is attenuated and confers protection against wild-type challenge in BALB/c mice
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布鲁氏菌 M5-90 磷酸葡萄糖变位酶 (PGM) 突变体被减弱，并为 BALB/c 小鼠提供针对野生型攻击的保护
DOI：
10.1007/s11274-016-2015-6
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发表时间：
2016-04-01
影响因子：
4.1
通讯作者：
Zhang, Hui
中科院分区：
文献类型：
--
作者：
Zhang, Yu;Li, Tiansen;Zhang, Hui
布鲁氏菌是革兰氏阴性细胞内细菌病原体，感染人类和动物，给发展中国家带来巨大的经济负担。布鲁氏菌减毒活疫苗（M5-90株或其他）是预防和控制动物布鲁氏菌病的最有效手段。然而，这些疫苗有几个缺点，包括在动物中残留的毒力，以及难以区分自然感染和疫苗免疫，这限制了它们的应用。一种能够区分感染和免疫的疫苗将有广泛的应用。羊种布鲁氏菌（Brucella melitensis，B. Melitensis）菌株M5-90 pgm突变体（M5-90Δpgm）的构建克服了这些缺点。M5-90Δpgm在胚胎滋养层细胞和小鼠中的存活率显著降低，并在BALB/c小鼠中诱导高保护性免疫。此外，M5-90Δpgm引发抗布鲁氏菌特异性免疫球蛋白G应答，并诱导γ干扰素（IFN-γ）和白细胞介素-2（IL-2）分泌。此外，M5-90Δpgm还能诱导免疫绵羊分泌IFN-γ。通过虎红平板试验（RBPT）和标准试管凝集试验（STAT），接种M5-90Δpgm的绵羊血清样本呈阴性。此外，PGM抗原允许感染和接种动物之间的血清学区分。这些结果表明，M5-90Δpgm是一种理想的抗B减毒活疫苗候选物。melitensis 16 M，值得进一步评价疫苗开发。
Brucellae are Gram-negative intracellular bacterial pathogens that infect humans and animals, bringing great economic burdens to developing countries. Live attenuated Brucella vaccines (strain M5-90 or others) are the most efficient means for prevention and control of animal brucellosis. However, these vaccines have several drawbacks, including residual virulence in animals, and difficulties in differentiating natural infection from vaccine immunization, which limit their application. A vaccine that can differentiate infection from immunization will have extensive applications. A Brucella melitensis (B. melitensis) strain M5-90 pgm mutant (M5-90Δpgm) was constructed to overcome these drawbacks. M5-90Δpgm showed significantly reduced survival in embryonic trophoblast cells and in mice, and induced high protective immunity in BALB/c mice. Moreover, M5-90Δpgm elicited an anti-Brucella-specific immunoglobulin G response and induced the secretion of gamma interferon (IFN-γ) and interleukin-2 (IL-2). In addition, M5-90Δpgm induced the secretion of IFN-γ in immunized sheep. Serum samples from sheep inoculated with M5-90Δpgm were negative by the Rose Bengal Plate Test (RBPT) and Standard Tube Agglutination Test (STAT). Furthermore, the PGM antigen allowed serological differentiation between infected and vaccinated animals. These results suggest that M5-90Δpgm is an ideal live attenuated vaccine candidate against B. melitensis 16 M and deserves further evaluation for vaccine development.