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通过黏膜和皮下免疫肺炎球菌 SP0148 蛋白预防致命性肺炎。

Protection against fatal pneumonia through mucosal and subcutaneous immunization with the pneumococcal SP0148 protein.

机构信息

Department of Laboratory Medicine, The First Affiliated Hospital, Zunyi Medical University, Zunyi, 563003, China.

Department of Blood Transfusion, The First Affiliated Hospital, Zunyi Medical University, Zunyi, 563003, China.

出版信息

Microb Pathog. 2019 Apr;129:206-212. doi: 10.1016/j.micpath.2019.02.018. Epub 2019 Feb 14.

Abstract

Streptococcus pneumoniae infection is associated with very high morbidity and mortality throughout the world. Vaccines are an effective measure for the reduction of S. pneumoniae infection. In particular, protein vaccines are attracting increasing attention because of their good immunogenicity and wide coverage of serotypes. Therefore, identifying effective protein vaccine targets is important for protein vaccine development. SP0148 is a promising protein vaccine target for S. pneumoniae and is capable of reducing S. pneumoniae colonization in the nasopharynx of mice through the IL-17A pathway. However, the protective effects of SP0148 in fatal pneumococcal infection have not been evaluated. This study used subcutaneous and nasal immunization routes to systematically evaluate the protective effects of the SP0148 protein in fatal pneumococcal infection. Subcutaneous and nasal mucosal immunization with recombinant SP0148 protein produced effective immune protection against infection with a lethal dose of S. pneumoniae and significantly prolonged survival time and increased the survival rate of mice. Furthermore, nasal immunization with SP0148 induced mouse splenocytes to secrete high levels of the cytokines IFN-γ and IL-17A. Both recombinant SP0148 protein and its antiserum inhibited the adhesion of S.pneumoniae D39 to A549 human lung epithelial cells in a dose-dependent manner. In summary, SP0148 induced mice to produce protective immune responses to fatal S. pneumoniae infection, and our results could contribute to the accumulating data on the use of SP0148 protein vaccines.

摘要

肺炎链球菌感染在全球范围内发病率和死亡率都很高。疫苗是减少肺炎链球菌感染的有效措施。特别是,由于其良好的免疫原性和广泛的血清型覆盖范围,蛋白质疫苗越来越受到关注。因此,确定有效的蛋白质疫苗靶标对于蛋白质疫苗的开发非常重要。SP0148 是肺炎链球菌有前途的蛋白质疫苗靶标,能够通过 IL-17A 途径减少小鼠鼻咽部肺炎链球菌的定植。然而,SP0148 在致命性肺炎球菌感染中的保护作用尚未得到评估。本研究使用皮下和鼻内免疫途径系统评估了 SP0148 蛋白在致命性肺炎球菌感染中的保护作用。用重组 SP0148 蛋白进行皮下和鼻黏膜免疫接种可有效预防致死剂量肺炎链球菌感染,并显著延长存活时间,提高小鼠的存活率。此外,SP0148 鼻内免疫可诱导小鼠脾细胞分泌高水平的细胞因子 IFN-γ 和 IL-17A。重组 SP0148 蛋白及其抗血清均可剂量依赖性抑制肺炎链球菌 D39 与人肺上皮细胞 A549 的黏附。总之,SP0148 诱导小鼠对致命性肺炎链球菌感染产生保护性免疫反应,我们的结果可能有助于积累关于使用 SP0148 蛋白疫苗的数据。

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