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布鲁氏菌 abortus 外膜蛋白 16 的蛋白部分是一种新的细菌病原体相关分子模式,可在体内激活树突状细胞,诱导 Th1 免疫应答,是一种有前途的自身佐剂疫苗,可预防全身和口服布鲁氏菌病。

The protein moiety of Brucella abortus outer membrane protein 16 is a new bacterial pathogen-associated molecular pattern that activates dendritic cells in vivo, induces a Th1 immune response, and is a promising self-adjuvanting vaccine against systemic and oral acquired brucellosis.

机构信息

Laboratory of Immunogenetics, Clinical Hospital José de San Martín, School of Medicine, University of Buenos Aires, Buenos Aires.

出版信息

J Immunol. 2010 May 1;184(9):5200-12. doi: 10.4049/jimmunol.0902209. Epub 2010 Mar 29.

Abstract

Knowing the inherent stimulatory properties of the lipid moiety of bacterial lipoproteins, we first hypothesized that Brucella abortus outer membrane protein (Omp)16 lipoprotein would be able to elicit a protective immune response without the need of external adjuvants. In this study, we demonstrate that Omp16 administered by the i.p. route confers significant protection against B. abortus infection and that the protective response evoked is independent of the protein lipidation. To date, Omp16 is the first Brucella protein that without the requirement of external adjuvants is able to induce similar protection levels to the control live vaccine S19. Moreover, the protein portion of Omp16 (unlipidated Omp16 [U-Omp16]) elicits a protective response when administered by the oral route. Either systemic or oral immunization with U-Omp16 elicits a Th1-specific response. These abilities of U-Omp16 indicate that it is endowed with self-adjuvanting properties. The adjuvanticity of U-Omp16 could be explained, at least in part, by its capacity to activate dendritic cells in vivo. U-Omp16 is also able to stimulate dendritic cells and macrophages in vitro. The latter property and its ability to induce a protective Th1 immune response against B. abortus infection have been found to be TLR4 dependent. The facts that U-Omp16 is an oral protective Ag and possesses a mucosal self-adjuvanting property led us to develop a plant-made vaccine expressing U-Omp16. Our results indicate that plant-expressed recombinant U-Omp16 is able to confer protective immunity, when given orally, indicating that a plant-based oral vaccine expressing U-Omp16 could be a valuable approach to controlling this disease.

摘要

鉴于细菌脂蛋白的脂类部分具有固有刺激性,我们首先假设布鲁氏菌外膜蛋白(Omp)16 脂蛋白无需外部佐剂就能引发保护性免疫反应。在这项研究中,我们证明了通过腹腔途径给予 Omp16 可显著抵抗布鲁氏菌感染,并且所引发的保护反应与蛋白脂质化无关。迄今为止,Omp16 是第一个无需外部佐剂就能诱导与对照活疫苗 S19 相似保护水平的布鲁氏菌蛋白。此外,Omp16 的蛋白部分(未脂化的 Omp16 [U-Omp16])通过口服途径给药时也能引发保护反应。无论是全身免疫还是口服免疫 U-Omp16 都会引发 Th1 特异性反应。U-Omp16 的这些能力表明它具有自身佐剂特性。U-Omp16 的佐剂特性至少部分可以解释为其在体内激活树突状细胞的能力。U-Omp16 还能够在体外刺激树突状细胞和巨噬细胞。后者的特性及其诱导针对布鲁氏菌感染的保护性 Th1 免疫反应的能力被发现依赖于 TLR4。U-Omp16 是一种口服保护抗原并且具有黏膜自身佐剂特性,这一事实促使我们开发了一种表达 U-Omp16 的植物生产疫苗。我们的结果表明,当口服给予时,植物表达的重组 U-Omp16 能够赋予保护性免疫,表明表达 U-Omp16 的植物基口服疫苗可能是控制这种疾病的一种有价值的方法。

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