Tanu Arifur Rahman, Ashraf Mohammad Arif, Hossain Md Faruk, Ismail Md, Shekhar Hossain Uddin
Department of Biochemistry & Molecular Biology, University of Dhaka, Dhaka-1000, Bangladesh.
Bioinformation. 2014 Aug 30;10(8):480-6. doi: 10.6026/97320630010480. eCollection 2014.
This study aims to design epitope-based peptides for the utility of vaccine development by targeting outer membrane protein F (Omp F), because two available licensed vaccines, live oral Ty21a and injectable polysaccharide, are 50% to 80% protective with a higher rate of side effects. Conventional vaccines take longer time for development and have less differentiation power between vaccinated and infected cells. On the other hand, Peptide-based vaccines present few advantages over other vaccines, such as stability of peptide, ease to manufacture, better storage, avoidance of infectious agents during manufacture, and different molecules can be linked with peptides to enhance their immunogenicity. Omp F is highly conserved and facilitates attachment and fusion of Salmonella typhi with host cells. Using various databases and tools, immune parameters of conserved sequences from Omp F of different isolates of Salmonella typhi were tested to predict probable epitopes. Binding analysis of the peptides with MHC molecules, epitopes conservancy, population coverage, and linear B cell epitope prediction were analyzed. Among all those predicted peptides, ESYTDMAPY epitope interacted with six MHC alleles and it shows highest amount of interaction compared to others. The cumulative population coverage for these epitopes as vaccine candidates was approximately 70%. Structural analysis suggested that epitope ESYTDMAPY fitted well into the epitope-binding groove of HLA-C*12:03, as this HLA molecule was common which interact with each and every predicted epitopes. So, this potential epitope may be linked with other molecules to enhance its immunogenicity and used for vaccine development.
本研究旨在通过靶向外膜蛋白F（Omp F）设计基于表位的肽用于疫苗开发，因为现有的两种许可疫苗，即口服减毒活疫苗Ty21a和注射用多糖疫苗，保护率为50%至80%，且副作用发生率较高。传统疫苗开发时间较长，且在接种疫苗的细胞和感染细胞之间的区分能力较弱。另一方面，基于肽的疫苗比其他疫苗具有一些优势，例如肽的稳定性、易于生产、更好的储存性、生产过程中避免感染因子，并且不同分子可以与肽连接以增强其免疫原性。Omp F高度保守，有助于伤寒沙门氏菌与宿主细胞的附着和融合。使用各种数据库和工具，对不同伤寒沙门氏菌分离株Omp F保守序列的免疫参数进行测试以预测可能的表位。分析了肽与MHC分子的结合分析、表位保守性、群体覆盖率和线性B细胞表位预测。在所有预测的肽中，ESYTDMAPY表位与六个MHC等位基因相互作用，与其他表位相比显示出最高的相互作用量。这些作为候选疫苗的表位的累积群体覆盖率约为70%。结构分析表明，表位ESYTDMAPY很好地适配于HLA-C*12:03的表位结合槽，因为这种HLA分子是常见的，与每个预测的表位相互作用。因此，这种潜在表位可与其他分子连接以增强其免疫原性，并用于疫苗开发。
