Intradermal immunization with outer membrane protein 25 protects Balb/c mice from virulent B. abortus 544

Intradermal immunization with outer membrane protein 25 protects Balb/c mice from virulent B. abortus 544
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DOI:
10.1016/j.molimm.2012.02.126
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发表时间:
2012-06-01
影响因子:
3.6
通讯作者:
Bhatnagar, Rakesh
Bhatnagar, Rakesh
中科院分区:
医学3区
文献类型:
--
作者:
Goel, Divya;Bhatnagar, Rakesh

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流产布鲁氏菌是布鲁氏菌病的病原体,布鲁氏菌病是一种影响流行地区的人畜共患病,既感染家畜,也感染人类,因此构成潜在的生物恐怖威胁。外膜蛋白25在布鲁氏菌中是保守的。Omp 25突变株在小鼠体内表现出减毒作用,强调Omp 25在布鲁氏菌毒力中的作用。而且。Omp 25已显示抑制人巨噬细胞中TNF-α的产生,从而消除细胞介导的免疫。在这项研究中,我们评估了重组Omp 25的免疫原性潜力及其对强毒B的保护效力。Balb/c小鼠中的流产攻击。通过两种免疫途径施用重组Omp 25:腹膜内和皮内。与腹膜内免疫相比,皮内免疫观察到剂量减少。较高的IgG 1:IgG 2b比值表明两种免疫途径的免疫应答均存在较强的Th 2偏倚。免疫小鼠脾细胞的体外刺激导致高水平的IL-4沿着增加的IL-12和IFN-γ水平,表明混合的Th 1和Th 2型免疫应答。用强毒B攻击免疫小鼠。流产和脾定植B。皮内免疫小鼠的流产率显着降低。皮内免疫的保护作用与B相当。牛种S-19菌株。激发后脾匀浆中的细胞因子水平显示细胞介导的免疫应答,IL-12和IFN-γ水平升高,但IL-4的量不可检测。这可能是rOmp 25免疫后在小鼠中观察到的保护作用背后的一个可能原因。因此,我们的研究建议重组Omp 25是一个潜在的亚单位疫苗候选人对布鲁氏菌病。(c)2012爱思唯尔有限公司保留所有权利。
Brucella abortus is a causative agent of brucellosis, a zoonosis affecting the endemic areas, which infects domestic animals as well as humans, thus, posing a potential bioterror threat. Outer membrane protein 25 is conserved among the Brucella species. Omp25 mutant strain of Brucella is shown to be attenuated in mice emphasizing on the role of Omp25 in Brucella virulence. Moreover. Omp25 has been shown to inhibit TNF-alpha production in human macrophages, thereby, abrogating cell mediated immunity. In this study, we evaluated the immunogenic potential of recombinant Omp25 and its protective efficacy against virulent B. abortus challenge in Balb/c mice. Recombinant Omp25 was administered via two routes of immunization: intraperitoneal and intradermal. Dosage reduction was observed with intradermal immunization when compared with intraperitoneal immunization. A higher IgG1 :IgG2b ratio suggested a strong Th2 bias of immune response in both the routes of immunization. In vitro stimulation of splenocytes from immunized mice resulted in high level of IL-4 along with increasing levels of IL-12 and IFN-gamma indicating a mixed Th1 and Th2 type of immune response. Immunized mice were challenged with virulent B. abortus and splenic colonization of B. abortus reduced significantly in intradermally immunized mice. Intradermal immunization gave protection comparable to that of B. abortus S-19 strain. Cytokine levels in spleen homogenate after challenge revealed a cell mediated immune response with elevated levels of IL-12 and IFN-gamma but no detectable amount of IL-4. This can be a possible reason behind the protection observed in mice after rOmp25 immunization. Thus, our study proposes recombinant Omp25 to be a potential subunit vaccine candidate against brucellosis. (c) 2012 Elsevier Ltd. All rights reserved.