Zhang Yu, Li Tiansen, Zhang Jing, Li Zhiqiang, Zhang Yan, Wang Zhen, Feng Hanping, Wang Yuanzhi, Chen Chuangfu, Zhang Hui
College of Animal Science and Technology, Shihezi University, Shihezi, 832000, Xinjiang Province, People's Republic of China.
School of Life Sciences, Shangqiu Normal University, Shangqiu, 476000, Henan Province, People's Republic of China.
World J Microbiol Biotechnol. 2016 Apr;32(4):58. doi: 10.1007/s11274-016-2015-6. Epub 2016 Feb 29.
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.
布鲁氏菌是革兰氏阴性胞内细菌病原体，可感染人类和动物，给发展中国家带来巨大经济负担。减毒活布鲁氏菌疫苗（M5-90株或其他毒株）是预防和控制动物布鲁氏菌病最有效的手段。然而，这些疫苗存在一些缺点，包括在动物体内有残余毒力，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前景。为克服这些缺点，构建了一株羊种布鲁氏菌（B. melitensis）M5-90 pgm突变株（M5-90Δpgm）。M5-90Δpgm在胚胎滋养层细胞和小鼠体内的存活率显著降低，并在BALB/c小鼠中诱导出高保护性免疫力。此外，M5-90Δpgm引发了抗布鲁氏菌特异性免疫球蛋白G反应，并诱导了γ干扰素（IFN-γ）和白细胞介素-2（IL-2）的分泌。另外，M5-90Δpgm在免疫的绵羊中诱导了IFN-γ的分泌。接种M5-90Δpgm的绵羊血清样本经玫瑰红平板试验（RBPT）和标准试管凝集试验（STAT）检测为阴性。此外，PGM抗原可实现感染动物和接种疫苗动物的血清学鉴别。这些结果表明，M5-90Δpgm是一株针对羊种布鲁氏菌16M的理想减毒活疫苗候选株，值得在疫苗研发中进一步评估。
