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重组串联表位疫苗接种可在小鼠中提供针对胸膜肺炎放线杆菌攻击的交叉保护。

Recombinant tandem epitope vaccination provides cross protection against Actinobacillus pleuropneumoniae challenge in mice.

作者信息

Xiao Jiameng, Liu Jianfang, Bao Chuntong, Zhu Rining, Gu Jingmin, Sun Changjiang, Feng Xin, Du Chongtao, Han Wenyu, Li Yang, Lei Liancheng

机构信息

College of Veterinary Medicine/ Key Laboratory of Zoonosis, Institute of Zoonosis, Jilin University, Xi'an Road 5333, Changchun, 130062, Jilin, People's Republic of China.

出版信息

AMB Express. 2020 Jul 8;10(1):123. doi: 10.1186/s13568-020-01051-1.

Abstract

Actinobacillus pleuropneumoniae (A. pleuropneumoniae/APP) is the pathogen that causes porcine contagious pleuropneumonia. Actinobacillus pleuropneumoniae is divided into 18 serovars, and the cross protection efficacy of epitopes is debatable, which has resulted in the slow development of a vaccine. Consequently, epitope-based vaccines conferring Actinobacillus pleuropneumoniae cross protection have rarely been reported. In this study, B cell epitopes in the head domain of trimeric autotransporter adhesin were predicted, and 6 epitopes were selected. Then, the predicted epitopes (Ba1, Bb5, C1, PH1 and PH2) were connected by linkers to construct a recombinant tandem antigen (rta) gene. The RTA protein encoded by the recombinant rta gene was expressed, and finally the ICR mice were immunized with the RTA protein with or without inactivated Actinobacillus pleuropneumoniae (serovars 1 and 5b) and challenged with Actinobacillus pleuropneumoniae to evaluate the protective effect of the epitope-based vaccine and combined vaccine. The mice in the RTA-immunized group and RTA plus inactivated Actinobacillus pleuropneumoniae vaccine group had a significant improvement in clinical symptoms and a higher level of antibody in the serum than those in the control group. The RTA immune group had a 40% survival rate after Actinobacillus pleuropneumoniae infection, whereas the combination of RTA and inactivated Actinobacillus pleuropneumoniae produced very strong cross immune protection in mice, at least 50% (RTA IB1 + C5) and at most 100% (RTA IB5 + C1), whereas no cross immunoprotection was found in the solo Actinobacillus pleuropneumoniae immune group. Overall, the combination of the RTA protein and inactivated bacteria significantly enhanced the cross protection effects. This implies that RTA protein in combination with a suitable inactivated Actinobacillus pleuropneumoniae strain could be a candidate vaccine for porcine contagious pleuropneumonia.

摘要

猪胸膜肺炎放线杆菌(A. pleuropneumoniae/APP)是引起猪传染性胸膜肺炎的病原体。猪胸膜肺炎放线杆菌分为18个血清型,表位的交叉保护效力存在争议,这导致疫苗研发进展缓慢。因此,很少有关于赋予猪胸膜肺炎放线杆菌交叉保护的基于表位的疫苗的报道。在本研究中,预测了三聚体自转运黏附素头部结构域中的B细胞表位,并选择了6个表位。然后,通过连接子连接预测的表位(Ba1、Bb5、C1、PH1和PH2)以构建重组串联抗原(rta)基因。表达重组rta基因编码的RTA蛋白,最后用RTA蛋白免疫ICR小鼠,同时使用或不使用灭活的猪胸膜肺炎放线杆菌(血清型1和5b),并用猪胸膜肺炎放线杆菌进行攻毒,以评估基于表位的疫苗和联合疫苗的保护效果。RTA免疫组和RTA加灭活猪胸膜肺炎放线杆菌疫苗组的小鼠临床症状有显著改善,血清中抗体水平高于对照组。RTA免疫组在感染猪胸膜肺炎放线杆菌后存活率为40%;而RTA与灭活猪胸膜肺炎放线杆菌联合使用在小鼠中产生了非常强的交叉免疫保护,最低为50%(RTA IB1 + C5),最高为100%(RTA IB5 + C1),而单独的猪胸膜肺炎放线杆菌免疫组未发现交叉免疫保护。总体而言,RTA蛋白与灭活细菌联合使用显著增强了交叉保护效果。这意味着RTA蛋白与合适的灭活猪胸膜肺炎放线杆菌菌株联合使用可能是猪传染性胸膜肺炎的候选疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/254e/7343699/4a1f25bcb65d/13568_2020_1051_Fig1_HTML.jpg

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