Immunoinformatics aided design of a new epitope-based vaccine candidate targeting pneumococcal histidine triad protein D (PhtD)
- سال انتشار: 1402
- محل انتشار: بیست و چهارمین کنگره بین المللی میکروب شناسی ایران
- کد COI اختصاصی: MEDISM24_664
- زبان مقاله: انگلیسی
- تعداد مشاهده: 153
نویسندگان
Department of Medical Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran Department of Microbiology, Pasteur Institute of Iran, Tehran,
Department of Medical Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran Department of Microbiology, Pasteur Institute of Iran, Tehran,
Department of Medical Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran۲ Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran Drug Design and Bioinformatics Unit, Department of Medical Bio
Razi Vaccine and Serum Research Institute, Agricultural Research, Education, and Extension Organization (AREEO), Karaj, Iran
Department of Medical Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran۲ Biotechnology Research Center, Semnan University of Medical Sciences, Semnan, Iran
Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran
چکیده
BACKGROUND AND OBJECTIVESStreptococcus pneumoniae (pneumococcus) is a major respiratory pathogen that causes high levels of mortality and morbidity in infants and the elderly. Despite the use of antibiotics and vaccines, fatal pneumococcal disease remains prevalent. Due to drawbacks of the current polysaccharide-based vaccine, the most promising way to generate an improved vaccine may be to utilize pneumococcal protein antigens with different roles in virulence. Pneumococcal histidine triad protein D (PhtD), a highly immunogenic surface protein produced by all strains of S. pneumoniae, can elicit protective immunity against fatal pneumococcal infections.MATERIALS AND METHODSIn this study, immunoinformatics approach was used to design an effective epitope-based vaccine against pneumococcal strains based on PhtD protein. The high-scored B- and T-cell epitopes overlapping with each other shared between different servers were considered, and the final peptides from PhtD protein were linked together with suitable linker. The prediction of the physicochemical and immunological properties, antigenicity, allergenicity, toxicity, ۳D model, and structural B cell epitopes in the final construct, as well as molecular docking of the final model with HLA receptor and immune simulation were carried out using computational tools.RESULTS AND DISCUSSIONThe evaluation of the characteristics showed that the final construct is stable, soluble, antigenic and non-allergenic. In addition, it was found that the protein has an acidic and hydrophilic nature. The ۳D model was constructed and refined, and the Ramachandran plot, ProSA-web and ERRAT confirmed the quality of the final model. Molecular docking analysis showed that the developed construct could strongly interact with HLA receptor. Finally, codon adaptation was performed for gene expression in E. coli followed by in silico cloning in the pET۲۸a(+) plasmid. Computational analysis revealed that the designed construct passed the evaluations with satisfactory scores and had the potential to induce robust immune responses.CONCLUSIONFor the first time, this study presents a new vaccine containing the dominant epitopic regions of the PhtD antigen. In silico analysis showed acceptable results, however, the proposed vaccine candidate should be experimentally verified in the laboratory to ensure its safety and immunogenicity.کلیدواژه ها
Streptococcus pneumoniae, Pneumococcal histidine triad protein D (PhtD), computational tools, Immunoinformatics, epitope-based vaccine candidateمقالات مرتبط جدید
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