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基于乳球菌的布鲁氏菌病疫苗:rOmp16-IL2 融合蛋白在小鼠中的 IgG 免疫应答。

Lactococcus-based vaccine against brucellosis: IgG immune response in mice with rOmp16-IL2 fusion protein.

机构信息

Department of Cell & Molecular Biology and Microbiology, Faculty of Science and Biotechnology, University of Isfahan, 817467344, Isfahan, Islamic Republic of Iran.

Molecular and Medicine Research Center, Arak University of Medical Science, Arak, Islamic Republic of Iran.

出版信息

Arch Microbiol. 2021 Jul;203(5):2591-2596. doi: 10.1007/s00203-021-02241-6. Epub 2021 Mar 10.

DOI:10.1007/s00203-021-02241-6
PMID:33689001
Abstract

This study was designed to introduce the recombinant Lactococcus lactis MG1363 as a cell factory candidate for production of recombinant Brucella melitensis Omp16-Human IL2 (r-Omp16-IL2) and to suggest it as a promising safe, non-pathogenic mucosal live vaccine against brucellosis. Three groups of BALB/c mice (10 mice per group) were intragastrically administrated with phosphate-buffered saline (PBS), L. lactis harboring the empty pAMJ2008 plasmid and with L. lactis expressing rOmp-IL2. The first two groups were classified as control groups and the third one is indicated as treatment group. Another group was injected by the intraperitoneal (i.p.) route with purified rOmp16-IL2 protein. The total serum IgG of each group was assessed with indirect ELISAs at two days before immunization and also two weeks after the last immunization. Results showed that BALB/c mice intragastrically administrated with L. lactis expressing rOmp-IL2 had dominant IgG response compared to the control (PBS administrated) group (P < 0.05). The level of IgG was significantly increased by intraperitoneally injection of recombinant Omp-IL2 in adjuvant compared to the intragastrically administration of PBS and L. lactis/pAMJ2008 as control groups, and also compared to L. lactis/pAMJ2008-rOmp-IL2 (P < 0.05). Our findings provide the use of L. lactis rOmp16-IL2 as a new promising alternative safe strategy than presently live attenuated vaccines toward developing an oral vaccine or subunit-based vaccine against brucellosis.

摘要

本研究旨在介绍重组乳球菌 MG1363 作为生产重组布鲁氏菌 melitensis Omp16-人 IL2(r-Omp16-IL2)的细胞工厂候选物,并将其作为一种有前途的安全、非致病性黏膜活疫苗来预防布鲁氏菌病。将三组 BALB/c 小鼠(每组 10 只)分别经胃内给予磷酸盐缓冲盐水(PBS)、携带空 pAMJ2008 质粒的乳球菌和表达 rOmp-IL2 的乳球菌。前两组被归类为对照组,第三组为治疗组。另一组通过腹腔内(i.p.)途径注射纯化的 rOmp16-IL2 蛋白。在免疫前两天和最后一次免疫后两周,用间接 ELISA 评估每组的总血清 IgG。结果表明,与对照组(PBS 组)相比,经胃内给予表达 rOmp-IL2 的乳球菌的 BALB/c 小鼠具有优势 IgG 反应(P<0.05)。与腹腔内给予 PBS 和 L. lactis/pAMJ2008 作为对照组相比,腹腔内给予重组 Omp-IL2 在佐剂中的 IgG 水平显著升高,与经胃内给予 PBS 和 L. lactis/pAMJ2008 相比,与 L. lactis/pAMJ2008-rOmp-IL2 相比,差异均有统计学意义(P<0.05)。我们的研究结果为使用乳球菌 rOmp16-IL2 提供了一种新的有前途的替代安全策略,而不是目前的减毒活疫苗,以开发针对布鲁氏菌病的口服疫苗或亚单位疫苗。

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本文引用的文献

1
Systems biology and bioinformatics help decipher Brucella antigens involved in clinical manifestation of the disease.系统生物学和生物信息学有助于破译布鲁氏菌病临床表现中涉及的抗原。
Front Cell Infect Microbiol. 2012 Mar 21;2:34. doi: 10.3389/fcimb.2012.00034. eCollection 2012.
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Interactions between professional phagocytes and Brucella spp.专业吞噬细胞与布鲁氏菌属之间的相互作用
Microbiologia. 1996 Jun;12(2):197-206.
基于多表位融合蛋白的间接酶联免疫吸附测定法用于人类布鲁氏菌病诊断的建立
PLoS Negl Trop Dis. 2025 Apr 7;19(4):e0012995. doi: 10.1371/journal.pntd.0012995. eCollection 2025 Apr.
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Oral vaccination with novel Lactococcus lactis mucosal live vector-secreting Brucella lumazine synthase (BLS) protein induces humoral and cellular immune protection against Brucella abortus.口服新型乳球菌黏膜活载体分泌布鲁氏菌尿苷酸合成酶(BLS)蛋白疫苗可诱导抗流产布鲁氏菌的体液和细胞免疫保护。
Arch Microbiol. 2023 Mar 20;205(4):122. doi: 10.1007/s00203-023-03471-6.
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Use of genetically modified lactic acid bacteria and bifidobacteria as live delivery vectors for human and animal health.利用基因工程改造的乳酸菌和双歧杆菌作为人类和动物健康的活体传递载体。
Gut Microbes. 2022 Jan-Dec;14(1):2110821. doi: 10.1080/19490976.2022.2110821.