A novel in silico minigene vaccine based on CD4+ T-helper and B-cell epitopes of EG95 isolates for vaccination against cystic echinococcosis |
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| Institution: | 1. Department of Animal Sciences, Faculty of Agriculture, University of Tabriz, Tabriz, Iran;2. Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran;3. School of Advanced Biomedical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran;4. Research Center for Infectious and Tropical Diseases, Tabriz University of Medical Sciences, Tabriz, Iran;5. Department of Pathobiology, Veterinary College, University of Tabriz, Tabriz, Iran;6. Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran;1. State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, CAAS, Lanzhou 730046, China;2. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China;1. Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, Xinjiang, PR China;2. Department of Clinical Laboratory, The Third Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, Xinjiang, PR China;3. Department of Immunology, College of Basic Medicine, Xinjiang Medical University, Urumqi 830011, Xinjiang, PR China;1. The Hopkirk Research Institute, AgResearch Ltd, Private Bag 11-008, Palmerston North, New Zealand;2. School of Pharmacy, University of Otago, PO Box 56, Dunedin, New Zealand;1. Fundamental and Applied Research for Animals and Health (FARAH), University of Liege, Belgium;2. Department of Pathology and Veterinary Public Health, Parasitological Unit, Agronomic and Veterinary Institute Hassan II, Rabat, Morocco;3. National School of Public Health, Ministry of Health, Rabat, Morocco;4. Integrated Veterinary Research Unit, Department of Veterinary Medicine, University of Namur, Belgium;5. Department of Vaccinology, Faculty of Medicine and Health Sciences, University of Antwerp, Belgium |
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| Abstract: | EG95 oncospheral antigen plays a crucial role in Echinococcus granulosus pathogenicity. Considering the diversity of antigen among different EG95 isolates, it seems to be an ideal antigen for designing a universal multivalent minigene vaccine, so-called multi-epitope vaccine. This is the first in silico study to design a construct for the development of global EG95-based hydatid vaccine against E. granulosus in intermediate hosts. After antigen sequence selection, the three-dimensional structure of EG95 was modeled and multilaterally validated. The preliminary parameters for B-cell epitope prediction were implemented such as the possible transmembrane helix, signal peptide, post-translational modifications and allergenicity. The high ranked linear and conformational B-cell epitopes derived from several online web-servers (e.g., ElliPro, BepiPred v1.0, BcePred, ABCpred, SVMTrip, IEDB algorithms, SEPPA v2.0 and Discotope v2.0) were utilized for multiple sequence alignment and then for engineering the vaccine construct. T-helper based epitopes were predicted by molecular docking between the high frequent ovar class II allele (Ovar-DRB1*1202) and hexadecamer fragments of the EG95 protein. Having used the immune-informatics tools, we formulated the first EG95-based minigene vaccine based on T-helper epitope with high-binding affinity to the ovar MHC allele. This designed construct was analyzed for different physicochemical properties. It was also codon-optimized for high-level expression in Escherichia coli k12. Taken all, we propose the present in silico vaccine constructs as a promising platform for the generation of broadly protective vaccines for species and genus-specific immunization of the natural hosts of the parasite. |
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| Keywords: | EG95 T-helper epitope Ovar leukocyte antigen Docking B-cell epitope Minigene vaccine |
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