TgVax452, an epitope-based candidate vaccine targeting Toxoplasma gondii tachyzoite-specific SAG1-related sequence (SRS) proteins: immunoinformatics, structural simulations and experimental evidence-based approaches
Hamidreza Majidiani, Mohammad M. Pourseif, Bahareh Kordi, Mohammadreza Taban Sadeghi, Alireza Najafi
Abstract
BACKGROUND: The highly expressed surface antigen 1 (SAG1)-related sequence (SRS) proteins of T. gondii tachyzoites, as a widespread zoonotic parasite, are critical for host cell invasion and represent promising vaccine targets. In this study, we employed a computer-aided multi-method approach for in silico design and evaluation of TgVax452, an epitope-based candidate vaccine against T. gondii tachyzoite-specific SRS proteins. METHODS: Using immunoinformatics web-based tools, structural modeling, and static/dynamic molecular simulations, we identified and screened B- and T-cell immunodominant epitopes and predicted TgVax452's antigenicity, stability, safety, adjuvanticity, and physico-chemical properties. RESULTS: KJ/mol) between the TLR4 agonist residues (RS09 peptide) of the TgVax452 in interaction with human TLR4, potentially activating innate immune responses. Also, a dramatic increase was observed in specific antibodies (IgM and IgG), cytokines (IFN-γ), and lymphocyte responses, based on C-ImmSim outputs. Finally, we optimized TgVax452's codon adaptation and mRNA secondary structure for efficient expression in E. coli BL21 expression machinery. CONCLUSION: Our findings suggest that TgVax452 is a promising candidate vaccine against T. gondii tachyzoite-specific SRS proteins and requires further experimental studies for its potential use in preclinical trials.