Streptococcus pneumoniae is the main cause of diseases such as meningitis, pneumoniae and sepsis, especially in children and old people. Due to costly antibiotic treatment, and increasing resistance of pneumococcus, developing high-efficient protective vaccine against this pathogen is an urgent need. Although the pneumoniae polysaccharide vaccine (PPV) and pneumonia conjugate vaccines (PCV) are the efficient pneumococcal vaccine in children and adult groups, but the serotype replacement of S. pneumoniae strains causes the reduction in efficacy of such vaccines. For overcoming the aforesaid drawbacks epitope-based vaccines are introduced as the relevant alternative. In our previous research, the epitope vaccine was designed based on immunodominant epitopes from PspA, CbpA antigens as cellular stimulants and PhtD, PiuA as humoral stimulants. Because the low immunogenicity is the main disadvantage of epitope vaccine, in the current study, we applied coiled-coil self-assembled structures for developing our vaccine. Recently, self-assembled peptide nanoparticles (SAPNs) have gained much attention in the field of vaccine development due to their multivalency, self-adjuvanticity, biocompatibility, and size similarity to pathogen. In this regard, the final designed vaccine is comprised of cytotoxic T lymphocytes (CTL) epitopes from PspA and CbpA, helper T lymphocytes (HTL) epitopes from PhtD and PiuA, the pentamer and trimmer oligomeric domains form 5-stranded and 3-stranded coiled-coils as self-assembled scaffold, Diphtheria toxoids (DTD) as a universal T-helper, which fused to each other with appropriate linkers. The four different arrangements based on the order of above-mentioned compartments were constructed, and each of them were modeled, and validated to find the 3D structure. The structural, physicochemical, and immunoinformatics analyses of final vaccine construct represented that our vaccine could stimulate potent immune response against S. pneumoniae; however, the potency of that should be approved via various in vivo and in vitro immunological tests.

中文翻译：

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设计针对肺炎链球菌的自组装肽纳米疫苗：计算机策略。

肺炎链球菌是引起脑膜炎，肺炎和败血症等疾病的主要原因，尤其是在儿童和老年人中。由于昂贵的抗生素治疗和增加的肺炎球菌耐药性，迫切需要开发针对这种病原体的高效保护性疫苗。尽管肺炎链球菌多糖疫苗（PPV）和肺炎共轭疫苗（PCV）是儿童和成人人群中有效的肺炎球菌疫苗，但肺炎链球菌菌株的血清型替代导致此类疫苗效力下降。为了克服上述缺点，引入基于表位的疫苗作为相关替代方案。在我们先前的研究中，基于PspA，CbpA抗原作为细胞刺激剂和PhtD，PiuA作为体液刺激剂的免疫优势表位设计了表位疫苗。由于免疫原性低是表位疫苗的主要缺点，因此在当前研究中，我们将卷曲螺旋自组装结构用于开发我们的疫苗。近来，自组装的肽纳米颗粒（SAPNs）由于其多价，自佐性，生物相容性和与病原体的大小相似性而在疫苗开发领域引起了广泛关注。在这方面，最终设计的疫苗包括PspA和CbpA的细胞毒性T淋巴细胞（CTL）表位，PhtD和PiuA的辅助T淋巴细胞（HTL）表位，五链和三链卷曲的五聚体和三聚体寡聚域-线圈作为自组装支架，白喉类毒素（DTD）作为通用T辅助物，通过适当的接头彼此融合。根据上述隔室的顺序构建了四个不同的布置，并对每个模型进行了建模，并进行了验证以找到3D结构。最终疫苗构建体的结构，物理化学和免疫信息学分析表明，我们的疫苗可以刺激针对肺炎链球菌的有效免疫反应。然而，其效力应通过各种体内和体外免疫学试验来证实。