Anaplasma marginale type IV secretion system proteins VirB2, VirB7, VirB11, and VirD4 are immunogenic components of a protective bacterial membrane vaccine.
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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边缘无形体 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。
DOI：
10.1128/iai.01207-09
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发表时间：
2010
影响因子：
3.1
通讯作者：
Brown,WendyC
中科院分区：
文献类型：
--
作者：
Sutten,EricL;Norimine,Junzo;Beare,PaulA;Heinzen,RobertA;Lopez,JobE;Morse,Kaitlyn;Brayton,KellyA;Gillespie,JosephJ;Brown,WendyC
无形体和相关埃利希体属。是牲畜和人类重要的蜱传革兰氏阴性细菌病原体，可引起急性感染和疾病，并可能持续存在。用富含外膜（OM）的边缘无形体对牛进行免疫可以提供针对疾病和持续感染的完全保护。 OM 疫苗接种者对 OM 蛋白质组的血清学反应此前已鉴定出 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，这三种蛋白质还刺激 OM 疫苗接种者的 CD4+T 细胞反应。 T4SS 由跨越某些细菌内膜和外膜的蛋白质复合物组成，是一种重要的毒力因子，但作为疫苗靶点相对而言尚未被探索。本研究的目的是确定额外的 T4SS 蛋白对于用 A 的保护性 OM 部分免疫的动物是否具有免疫原性。筛选了体外转录和翻译表达的T4SS蛋白，用于刺激OM疫苗接种者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，并验证了其免疫原性。 VirB2、推定的 VirB7、VirB11 和 VirD4 对于表达几种常见主要组织相容性复合体 (MHC) II 类单倍型的 OM 疫苗接种者具有免疫原性。 VirB2 由共享一个保守中心区域的多个基因编码，表位作图揭示了该区域的 T 细胞表位。具有常见 MHC 单倍型的远交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 评估为致病菌的潜在候选疫苗的合理性。
Anaplasmaand relatedEhrlichiaspp. 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 anAnaplasma marginalefraction 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 ofA. marginale.T4SS proteins expressed byin vitrotranscription and translation were screened for stimulating proliferation of T cells from OM vaccinees, and immunogenic proteins were expressed as recombinant proteins inEscherichia coliand 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.