A novel in silico minigene vaccine based on CD4+ T-helper and B-cell epitopes of EG95 isolates for vaccination against cystic echinococcosis

• Published in: Computational biology and chemistry 2018-02, Vol.72, p.150-163
• Main Authors: Pourseif, Mohammad M., Moghaddam, Gholamali, Naghili, Behrouz, Saeedi, Nazli, Parvizpour, Sepideh, Nematollahi, Ahmad, Omidi, Yadollah
• Format: Article
• Language: English
• Subjects: B-cell epitope; Docking; EG95; Minigene vaccine; Ovar leukocyte antigen; T-helper epitope
• ISSN: 1476-9271; 1476-928X
• DOI: 10.1016/j.compbiolchem.2017.11.008

[Display omitted] •An in silico multiepitope sheep-specific vaccine was designed based on ovar MHC class II alleles.•Comprehensive computational methodologies was applied for the construction of minigene vaccine against E. granulosus.•In silico epitope mapping tools were used for the identification of B-cell and helper T-cell epitopes.•Various sequences of Eg95 from different geographical regions was used for greater coverage. 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.