Abstract
Human toxoplasmosis is a global public health concern and a commercial vaccine is still lacking. The present in silico study was done to design a novel vaccine candidate using tachyzoite-specific SAG1-realted sequence (SRS) proteins. Overlapping B-cell and strictly-chosen human MHC-I binding epitopes were predicted and connected together using appropriate spacers. Moreover, a TLR4 agonist, human high mobility group box protein 1 (HMGB1), and His-tag were added to the N- and C-terminus of the vaccine sequence. The final vaccine had 442 residues and a molecular weight of 47.71 kDa. Physico-chemical evaluation showed a soluble, highly antigenic and non-allergen protein, with coils and helices as secondary structures. The vaccine 3D model was predicted by ITASSER server, subsequently refined and was shown to possess significant interactions with human TLR4. As well, potent stimulation of cellular and humoral immunity was demonstrated upon chimeric vaccine injection. Finally, the outputs showed that this vaccine model possesses top antigenicity, which could provoke significant cell-mediated immune profile including IFN-γ, and can be utilized towards prophylactic purposes.
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The authors appreciate the staff of zoonotic diseases research center Ilam University of Medical Sciences, Ilam, Iran for their kind assistance in preparation of this manuscript.
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MS and NN conceived the study idea and protocol; HH, MCB and EG performed bioinformatics analyses, vaccine construction and subsequent validations; BNG and HM drafted the manuscript; HI performed docking analysis; MS and NN critically revised the work. All authors read and approved the final version.
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Shams, M., Heydaryan, S., Bashi, M.C. et al. In silico design of a novel peptide-based vaccine against the ubiquitous apicomplexan Toxoplasma gondii using surface antigens. In Silico Pharmacol. 11, 5 (2023). https://doi.org/10.1007/s40203-023-00140-w
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DOI: https://doi.org/10.1007/s40203-023-00140-w