College of Agroforestry Engineering and Planning (Cultural and Technological Industry Innovation Research Center), Tongren University, Tongren 554300, Guizhou, China; College of Animal Science and Technology, Zhejiang University, Hangzhou 3100204, Zhejiang, China.
College of One Health, Tongren University, Tongren 554300, Guizhou, China.
Microb Pathog. 2017 Nov;112:148-155. doi: 10.1016/j.micpath.2017.09.016. Epub 2017 Sep 12.
Brucellosis is a globally distributed zoonotic disease that causes animal and human diseases. Although effective, the current Brucella vaccines (strain M5-90 or others) have several drawbacks. The first is their residual virulence for animals and humans and the second is their inability to differentiate natural infection from that caused by vaccination. In the present study, Brucella melitensis M5-90 manB mutant (M5-90ΔmanB) was generated to overcome these drawbacks. M5-90ΔmanB showed significantly reduced survival in macrophages and mice, and induced strong protective immunity in BALB/c mice. It elicited anti-Brucella-specific IgG1 and IgG2a subtype responses and induced the secretion of gamma interferon (IFN-γ) and interleukin-4(IL-4). Results of immune assays showed, M5-90ΔmanB immunization induced the secretion of IFN-γ in goats, and serum samples from goats inoculated with M5-90ΔmanB were negative by Bengal Plate Test (RBPT) and Standard Tube Agglutination Test (STAT). Further, the ManB antigen also allows serological assays differentiate infections caused by wild strains from infections by vaccination. These results show that M5-90ΔmanB is a suitable attenuated vaccine candidate against virulent Brucella melitensis 16 M (16 M) infection.
布鲁氏菌病是一种分布广泛的动物源性传染病,可引起动物和人类疾病。虽然有效,但现有的布鲁氏菌疫苗(M5-90 株或其他株)存在几个缺点。第一个是它们对动物和人类的残余毒力,第二个是它们无法区分自然感染和疫苗接种引起的感染。在本研究中,生成了布鲁氏菌 M5-90 manB 突变体(M5-90ΔmanB)以克服这些缺点。M5-90ΔmanB 在巨噬细胞和小鼠中的存活能力显著降低,并在 BALB/c 小鼠中诱导出强烈的保护性免疫。它引起针对布鲁氏菌的特异性 IgG1 和 IgG2a 亚型反应,并诱导γ干扰素(IFN-γ)和白细胞介素-4(IL-4)的分泌。免疫检测结果表明,M5-90ΔmanB 免疫接种可诱导山羊分泌 IFN-γ,并且用孟加拉平板试验(RBPT)和标准试管凝集试验(STAT)检测接种 M5-90ΔmanB 的山羊血清样本均为阴性。此外,ManB 抗原还允许血清学检测区分由野生株引起的感染和由疫苗接种引起的感染。这些结果表明,M5-90ΔmanB 是一种针对强毒布鲁氏菌 16M(16M)感染的合适减毒疫苗候选株。