Development and in silico validation of a computationally designed, riboswitch controlled mRNA vaccine against chronic Toxoplasma gondii
Year: 2026
Type: article
Abstract: No licensed human vaccine exists for Toxoplasma gondii despite extensive research, due to the parasite’s intricate biochemistry and the significant challenge of targeting its persistent chronic form. This study aimed to develop a comprehensive immunoinformatics pipeline for the design and computational validation of a multi-epitope mRNA vaccine candidate against chronic toxoplasmosis. Immunodominant B-cell, cytotoxic T lymphocyte, and CD4 + T cell epitopes were computationally predicted and selected from three principal virulence antigens dense granule proteins (GRA25), apical membrane antigen 1 (AMA1), rhoptry kinases proteins (ROP43) using stringent criteria of antigenicity, non-allergenicity, and solubility. The vaccine construct incorporates; theophylline-responsive riboswitch, human IL-4 adjuvant, and DEC205 targeting domain. Validation relied on codon optimization, molecular docking against TLR7 and MHC class II, physicochemical characterization, systems immunology and immune simulation. According to the results, molecular docking confirmed strong binding affinities with target immune receptors. The innovative use of a riboswitch and dendritic cell (DC) targeting provides precise control over expression and enhanced immunogenicity. Ramachandran plots computationally validate the backbone conformation of docked vaccine constructs by mapping the dihedral angles for each amino acid residue. Immune simulation predicted robust, multifaceted responses characterized by, high antibody titers, Th1/Th2 cytokine secretion, and memory cell proliferation. The RNAfold server proved a stable structural MFE of -576.60 kcal/mol. Physicochemical analysis confirmed stability and solubility of the final vaccine construct. This integrated workflow spanning immunoinformatics, structural docking, and systems immunology yields a rationally designed, highly antigenic multi-epitope mRNA vaccine candidate and establishes a solid in silico framework for next-generation anti-parasitic therapeutics. However, these results are computational forecasts that necessitate experimental verification to establish immunogenicity and protection against T. gondii infection. Clinical trial number: Not applicable.
Source: Biology Direct
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,890
OpenAlex ID: W7225770159
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