Journal Article

TgVax452, an epitope-based candidate vaccine targeting Toxoplasma gondii tachyzoite-specific SAG1-related sequence (SRS) proteins: immunoinformatics, structural simulations and experimental evidence-based approaches

Pourseif, Mohammad M., Kordi, Bahareh, Majidiani, Hamidreza, Sadeghi, Mohammad-Reza, Najafi, Alireza

2024

Overview

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 The designed protein possessed 452 residues, a MW of 44.07 kDa, an alkaline pI (6.7), good stability (33.20), solubility (0.498), and antigenicity (0.9639) with no allergenicity. Comprehensive molecular dynamic (MD) simulation analyses confirmed the stable interaction (average potential energy: 3.3799 × 10 6 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Abortion / Accuracy / Adjuvanticity / Allergenicity / Allergens / Amino acids / Animals / Antibodies, Protozoan - immunology / Antigenic determinants / Antigenicity / Antigens, Protozoan - chemistry / Antigens, Protozoan - genetics / Antigens, Protozoan - immunology / CAD / Cell surface antigens / Chemical properties / Clinical trials / Codon / Computational Biology / Computer aided design / Dynamic simulations / E coli / Epitopes / Epitopes, B-Lymphocyte - chemistry / Epitopes, B-Lymphocyte - genetics / Epitopes, B-Lymphocyte - immunology / Epitopes, T-Lymphocyte - genetics / Epitopes, T-Lymphocyte - immunology / Escherichia coli / Female / Force and energy / Gene expression / Health aspects / Humans / Immune response / Immunodominant Epitopes - chemistry / Immunodominant Epitopes - genetics / Immunodominant Epitopes - immunology / Immunoglobulin G / Immunoglobulin M / Immunoinformatics / Infections / Infectious Diseases / Innate immunity / Internal Medicine / Lymphocytes / Lymphocytes T / Medical Microbiology / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Methods / Mice / Mice, Inbred BALB C / Molecular dynamics / Molecular Dynamics Simulation / Molecules / mRNA / Parasite vaccines / Parasites / Parasitology / Peptides / Pharmaceutical research / Physicochemical properties / Potential energy / Protein structure / Proteins / Protozoa / Protozoan Proteins - chemistry / Protozoan Proteins - genetics / Protozoan Proteins - immunology / Protozoan Vaccines - genetics / Protozoan Vaccines - immunology / Residues / Secondary structure / Simulation methods / SRS proteins / Stability / T cells / Tachyzoites / TLR4 protein / Toll-like receptors / Toxicity / Toxoplasma / Toxoplasma - chemistry / Toxoplasma - genetics / Toxoplasma - immunology / Toxoplasma Gondii / Toxoplasmosis - immunology / Toxoplasmosis - prevention & control / Tropical Medicine / Vaccines / Zoonoses / γ-Interferon