a Department of Pharmaceutical Biotechnology, School of Pharmacy , Shiraz University of Medical Sciences , Shiraz , Iran.
b Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences , Shiraz , Iran.
J Biomol Struct Dyn. 2019 Aug;37(13):3524-3535. doi: 10.1080/07391102.2018.1519460. Epub 2019 Jan 11.
is a leading cause of some diseases such as pneumonia, sepsis, and meningitis mostly in children less than 5 years of age. Presently, two types of pneumococcal vaccine are available on the market: polysaccharide vaccines (PPV) that are based on capsular polysaccharides of at least 92 different serotypes, and protein-conjugated polysaccharide vaccine (PCV). The PPVs such as PPV23 do not stimulate efficient protective immunity in children under 2 years old, while the PCVs such as PCV7, PCV10, and PCV13 that cover 7, 10, and 13 serotypes, respectively, highly protect newborns, but have some disadvantages such as complications in manufacturing, costly production, and also requires refrigeration and multiple injections. Epitope-based vaccines, including varied mixtures of conserved virulence proteins, are a promising alternative to the existing capsular antigen vaccines. In this study, it has been tried to design an efficient subunit vaccine in order to elicit both CTL and HTL responses. The immunodominant epitopes from highly protective antigens of (PspA, CbpA, PiuA, and PhtD) were selected from different databanks, such as IEDB, PROPRED, RANKPEP, and MHCPRED. The PspA and CbpA were chosen as CTL epitope stimulants, and PhtD and PiuA were defined as helper epitopes. Because of low immunogenicity of epitope vaccines, PorB protein as a TLR2 agonist was employed to increase the immunogenicity of the vaccine. All the peptide segments were fused to each other by proper linkers, and the physicochemical, structural, and immunological characteristics of the construct were also evaluated. To achieve a high-quality 3 D structure of the protein, modeling, refinement, and validation of the final construct were done. Docking and molecular dynamics analyses demonstrated an appropriate and stable interaction between the vaccine and TLR2 during the simulation period. The computational studies suggested the designed vaccine as a novel construct, capable to elicit efficient humoral and cellular immunities, which are crucial for protection against . Communicated by Ramaswamy H. Sarma.
是一些疾病的主要原因，如肺炎、败血症和脑膜炎，主要发生在 5 岁以下的儿童中。目前，市场上有两种类型的肺炎球菌疫苗：多糖疫苗 (PPV)，基于至少 92 种不同血清型的荚膜多糖，和蛋白结合多糖疫苗 (PCV)。PPV 如 PPV23 不能在 2 岁以下儿童中刺激有效的保护性免疫，而 PCV 如 PCV7、PCV10 和 PCV13 分别覆盖 7、10 和 13 种血清型，高度保护新生儿，但存在一些缺点，如制造并发症、生产成本高，还需要冷藏和多次注射。基于表位的疫苗，包括各种保守毒力蛋白的混合物，是现有荚膜抗原疫苗的一种有前途的替代方案。在这项研究中，试图设计一种有效的亚单位疫苗，以引起 CTL 和 HTL 反应。从高度保护性抗原 (PspA、CbpA、PiuA 和 PhtD) 中选择免疫优势表位，从不同的数据库，如 IEDB、PROPRED、RANKPEP 和 MHCPRED 中选择。PspA 和 CbpA 被选为 CTL 表位刺激物，而 PhtD 和 PiuA 被定义为辅助表位。由于表位疫苗的免疫原性低，PorB 蛋白作为 TLR2 激动剂被用于提高疫苗的免疫原性。所有肽段通过适当的接头彼此融合，并且还评估了构建体的物理化学、结构和免疫学特性。为了实现蛋白质的高质量 3D 结构，对最终构建体进行了建模、精修和验证。对接和分子动力学分析表明，在模拟过程中，疫苗和 TLR2 之间存在适当和稳定的相互作用。计算研究表明，所设计的疫苗是一种新型构建体，能够引发有效的体液和细胞免疫，这对于保护免受 至关重要。由 Ramaswamy H. Sarma 传达。
