首页> 外文期刊>Infection and immunity >Anaplasma marginale Type IV Secretion System Proteins VirB2, VirB7, VirB11, and VirD4 Are Immunogenic Components of a Protective Bacterial Membrane Vaccine
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Anaplasma marginale Type IV Secretion System Proteins VirB2, VirB7, VirB11, and VirD4 Are Immunogenic Components of a Protective Bacterial Membrane Vaccine

机译:边缘无浆膜IV型分泌系统蛋白VirB2,VirB7,VirB11和VirD4是保护性细菌膜疫苗的免疫原性成分。

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Anaplasma and related Ehrlichia spp. are important tick-borne, Gram-negative bacterial pathogens of livestock and humans that cause acute infection and disease and can persist. Immunization of cattle with an Anaplasma marginale fraction enriched in outer membranes (OM) can provide complete protection against disease and persistent infection. Serological responses of OM vaccinees to the OM proteome previously identified over 20 antigenic proteins, including three type IV secretion system (T4SS) proteins, VirB9-1, VirB9-2, and VirB10. Subsequent studies showed that these three proteins also stimulated CD4+ T-cell responses in OM vaccinees. The T4SS, composed of a complex of proteins spanning the inner and outer membranes of certain bacteria, is an important virulence factor but is relatively unexplored as a vaccine target. The goal of this study was to determine if additional T4SS proteins are immunogenic for animals immunized with the protective OM fraction of A. marginale. T4SS proteins expressed by in vitro transcription and translation were screened for stimulating proliferation of T cells from OM vaccinees, and immunogenic proteins were expressed as recombinant proteins in Escherichia coli and their immunogenicity was verified. VirB2, a putative VirB7, VirB11, and VirD4 were immunogenic for OM vaccinees expressing several common major histocompatibility complex (MHC) class II haplotypes. VirB2 is encoded by multiple genes that share a conserved central region, and epitope mapping revealed T-cell epitopes in this region. The discovery of novel immunogenic T4SS proteins recognized by outbred individuals with common MHC haplotypes further justifies evaluating the T4SS as a potential vaccine candidate for pathogenic bacteria.
机译:无浆膜和相关的埃里希氏菌 spp。是重要的由tick传播的牲畜和人类革兰氏阴性细菌病原体,可引起急性感染和疾病,并且可以持续存在。用富含外膜(OM)的 Anaplasma marginale 组分对牛进行免疫可为疾病和持续感染提供完全保护。 OM疫苗对OM蛋白质组的血清学反应先前鉴定出20多种抗原蛋白,包括三种IV型分泌系统(T4SS)蛋白,VirB9-1,VirB9-2和VirB10。随后的研究表明,这三种蛋白还可以刺激OM疫苗中的CD4 + T细胞反应。 T4SS由跨越某些细菌的内膜和外膜的蛋白质复合物组成,是一种重要的毒力因子,但尚未作为疫苗靶标进行开发。这项研究的目的是确定其他T4SS蛋白对于用 A保护性OM片段免疫的动物是否具有免疫原性。筛选了通过体外转录和翻译表达的T4SS蛋白,以刺激OM疫苗中T细胞的增殖,并在大肠杆菌中将免疫原性蛋白表达为重组蛋白。 em>,并验证了其免疫原性。 VirB2,推定的VirB7,VirB11和VirD4对表达几种常见的主要组织相容性复合体(MHC)II类单倍型的OM疫苗具有免疫原性。 VirB2由共享保守中心区域的多个基因编码,并且抗原决定簇定位揭示了该区域的T细胞抗原决定簇。具有常见MHC单倍型的近亲个体识别的新型免疫原性T4SS蛋白的发现进一步证明了将T4SS评估为潜在的致病细菌疫苗的合理性。

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