Identification of conserved surface proteins as novel antigenic vaccine candidates of Actinobacillus pleuropneumoniae
Identification of conserved surface proteins as novel antigenic vaccine candidates of Actinobacillus pleuropneumoniae
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胸膜肺炎放线杆菌新型抗原疫苗候选物保守表面蛋白的鉴定
DOI：
10.1007/s12275-012-2214-2
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发表时间：
2012-12-01
影响因子：
3
通讯作者：
Zhou, Rui
中科院分区：
文献类型：
--
作者：
Chen, Xiabing;Xu, Zhuofei;Zhou, Rui
胸膜肺炎放线杆菌是一种重要的猪呼吸道病原体，在世界范围内造成了巨大的经济损失。保守的表面抗原蛋白的鉴定有助于开发有效的疫苗。本研究采用全基因组策略，结合生物信息学和实验方法，发现并表征了胸膜肺炎假体表面相关的免疫原性蛋白。通过比较基因组学和基因表达谱分析，鉴定出39个编码外膜蛋白（OMPs）和脂蛋白的基因在不同血清型胸膜肺炎假单胞菌参考菌株中高度保守且转录稳定。在大肠杆菌中成功表达了其中12个保守蛋白，并在小鼠模型中通过同源激射评估了它们的免疫原性，然后通过同源和异源激射进一步测试了其中3个蛋白（APJL_0126、HbpA和OmpW）在自然宿主（猪）中的免疫原性。结果表明，这些蛋白可诱导高滴度抗体，但单独接种每种蛋白可诱导低保护性免疫。本研究为胸膜肺炎假体保守的omp和脂蛋白的免疫原性提供了新的见解。虽然本研究中表征的表面蛋白都不能单独诱导对胸膜肺炎假单胞菌的有效保护性免疫，但它们是与Apx毒素联合亚单位疫苗的潜在候选物。
Actinobacillus pleuropneumoniae is an important swine respiratory pathogen causing great economic losses worldwide. Identification of conserved surface antigenic proteins is helpful for developing effective vaccines. In this study, a genome-wide strategy combined with bioinformatic and experimental approaches, was applied to discover and characterize surface-associated immunogenic proteins of A. pleuropneumoniae. Thirty nine genes encoding outer membrane proteins (OMPs) and lipoproteins were identified by comparative genomics and gene expression profiling as being-highly conserved and stably transcribed in the different serotypes of A. pleuropneumoniae reference strains. Twelve of these conserved proteins were successfully expressed in Escherichia coli and their immunogenicity was estimated by homologous challenge in the mouse model, and then three of these proteins (APJL_0126, HbpA and OmpW) were further tested in the natural host (swine) by homologous and heterologous challenges. The results showed that these proteins could induce high titers of antibodies, but vaccination with each protein individually elicited low protective immunity against A. pleuropneumoniae. This study gives novel insights into immunogenicity of the conserved OMPs and lipoproteins of A. pleuropneumoniae. Although none of the surface proteins characterized in this study could individually induce effective protective immunity against A. pleuropneumoniae, they are potential candidates for subunit vaccines in combination with Apx toxins.