Immunogenicity and protective efficacy of recombinant Haemophilus parasuis SH0165 putative outer membrane proteins
Immunogenicity and protective efficacy of recombinant Haemophilus parasuis SH0165 putative outer membrane proteins
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重组副猪嗜血杆菌 SH0165 假定外膜蛋白的免疫原性和保护功效
DOI：
10.1016/j.vaccine.2012.11.003
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发表时间：
2013-01-02
期刊：
影响因子：
5.5
通讯作者：
Bei, Weicheng
中科院分区：
文献类型：
--
作者：
Fu, Shulin;Zhang, Minmin;Bei, Weicheng
副猪嗜血杆菌（Haemophilus parasuis，H.猪副猪嗜血杆菌（Parasuis）是引起猪多发性浆膜炎、多发性关节炎和脑膜炎的病原体，是世界范围内猪的最重要的细菌性疾病之一。目前几乎没有疫苗对所有致病性H.副猪。H.副猪嗜血杆菌推定的外膜蛋白（OMP）是更有效的疫苗的潜在必需组分。最近，H.本实验室完成了副猪血清型5株SH 0165的克隆，这使我们能够靶向OMP用于重组疫苗的开发。在本研究中，我们重点研究了10个推测的外膜蛋白，并将所有推测的外膜蛋白克隆、表达并纯化为HIS融合蛋白。在用LD 50激发的小鼠中进行免疫保护潜力的初步筛选。在这10种OMP中，发现三种融合蛋白rGAPDH、rOapA和rHPS-0675在H.副猪感染我们进一步评估了rGAPDH、rOapA和rHPS-0675在猪模型中的免疫应答和保护效力。所有三种蛋白质都能引起体液抗体应答，并对致死剂量的H.在猪模型中的副猪链球菌SH 0165。此外，针对三种单独蛋白质和协同蛋白质的抗血清在全血测定中有效地抑制细菌生长。数据表明，这三种蛋白单独显示出高价值，并且rGAPDH、rOapA和rHPS-0675的组合提供了最佳保护。我们的研究结果表明，rGAPDH，rOapA，和rHPS-0675诱导保护免受H。副猪链球菌SH 0165感染，这可能有助于多组分疫苗的开发。(C)2012爱思唯尔有限公司保留所有权利。
Haemophilus parasuis (H. parasuis), the causative agent of swine polyserositis, polyarthritis, and meningitis, is one of the most important bacterial diseases of pigs worldwide. Little vaccines currently exist that have a significant effect on infections with all pathogenic serovars of H. parasuis. H. parasuis putative outer membrane proteins (OMPs) are potentially essential components of more effective vaccines. Recently, the genomic sequence of H. parasuis serovar 5 strain SH0165 was completed in our laboratory, which allow us to target OMPs for the development of recombinant vaccines. In this study, we focused on 10 putative OMPs and all the putative OMPs were cloned, expressed and purified as HIS fusion proteins. Primary screening for immunoprotective potential was performed in mice challenged with an LD50 challenge. Out of these 10 OMPs three fusion proteins rGAPDH, rOapA, and rHPS-0675 were found to be protective in a mouse model of H. parasuis infection. We further evaluated the immune responses and protective efficacy of rGAPDH, rOapA, and rHPS-0675 in pig models. All three proteins elicited humoral antibody responses and conferred different levels of protection against challenge with a lethal dose of H. parasuis SH0165 in pig models. In addition, the antisera against the three individual proteins and the synergistic protein efficiently inhibited bacterial growth in a whole blood assay. The data demonstrated that the three proteins showed high value individually and the combination of rGAPDH, rOapA, and rHPS-0675 offered the best protection. Our results indicate that rGAPDH, rOapA, and rHPS-0675 induced protection against H. parasuis SH0165 infection, which may facilitate the development of a multi-component vaccine. (C) 2012 Elsevier Ltd. All rights reserved.