Toxoplasma gondii Microneme Protein 3 (TgMIC3): Computational Probing for Improved Vaccine Design
-
Masoud Foroutan
,
Hamidreza Majidiani
,
Fatemeh Ghaffarifar
,
Elaheh Karimzadeh-Soureshjani
,
Amir Karimipour-Saryazdi
,
Ali Dalir Ghaffari
,
John Horton
Abstract
Background: Microneme protein 3 (MIC3) is a key adhesion molecule in Toxoplasma gondii that is expressed during multiple stages of infection. We aimed to computationally characterize the immunological and structural features of the T. gondii MIC3 protein to assess its potential suitability as a vaccine candidate.
Methods: A comprehensive set of bioinformatics tools and web servers was employed to predict the physicochemical properties, allergenicity, antigenicity, solubility, post-translational modification sites, subcellular localization, transmembrane domains, signal peptides, secondary and tertiary structures, potential B- and T-lymphocyte epitopes, and simulated immune responses of the TgMIC3 protein.
Results: A total of 75 post-translational modification sites were predicted in TgMIC3. Furthermore, secondary structure analysis using GOR IV, SOPMA, and NetSurfP-3.0 indicated that random coils and extended strands were the predominant structural elements. In addition, several high-affinity B- and T-cell epitopes were identified across the protein sequence. Subsequent structural validation revealed that 82.91% and 98.60% of residues were located in favored regions in the initial and refined 3D models, respectively. The findings of the allergenicity and antigenicity assessments indicated that the MIC3 antigen seemed to be a non-allergen with an immunogenic nature. Moreover, immune simulation using the C-ImmSim server demonstrated that TgMIC3 could induce robust humoral and cell-mediated immune responses following three simulated antigen administrations.
Conclusion: This study provides foundational computational evidence supporting the potential of TgMIC3 as a vaccine antigen and offers a useful framework for future experimental investigations targeting vaccine development against acute and latent toxoplasmosis.
2. Dubey JP. The history of Toxoplasma gondii-the first 100 years. J Eukaryot Microbiol. 2008;55(6):467-75.
3. Dubey JP, Lindsay DS, Speer CA. Structures of Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts. Clin Microbiol Rev. 1998;11(2):267-99.
4. Weiss LM, Dubey JP. Toxoplasmosis: A history of clinical observations. Int J Parasitol. 2009;39(8):895-901.
5. Antczak M, Dzitko K, Dlugonska H. Human toxoplasmosis-Searching for novel chemotherapeutics. Biomed Pharmacother. 2016;82:677-84.
6. Zhang X, Yuan H, Mahmmod YS, et al. Insight into the current Toxoplasma gondii DNA vaccine: a review article. Expert Rev Vaccines. 2023;22(1):66-89.
7. Garcia-Reguet N, Lebrun M, Fourmaux MN, et al. The microneme protein MIC3 of Toxoplasma gondii is a secretory adhesin that binds to both the surface of the host cells and the surface of the parasite. Cell Microbiol. 2000;2(4):353-64.
8. Foroutan M, Zaki L, Ghaffarifar F. Recent progress in microneme-based vaccines development against Toxoplasma gondii. Clin Exp Vaccine Res. 2018;7(2):93-103.
9. Flower DR, Macdonald IK, Ramakrishnan K, Davies MN, Doytchinova IA. Computer aided selection of candidate vaccine antigens. Immunome Res. 2010; 6 Suppl 2(Suppl 2):S1.
10. Kazi A, Chuah C, Majeed ABA, Leow CH, Lim BH, Leow CY. Current progress of immunoinformatics approach harnessed for cellular- and antibody-dependent vaccine design. Pathog Glob Health. 2018;112(3):123-31.
11. Mohammadi MK, Dalir Ghaffari A. MIC13 of Toxoplasma gondii: Potential gene for vaccine candidate-an in silico approach. J Parasitol Res. 2025;2025:3114690.
12. Foroutan M, Elsheikha HM, Karimipour-Saryazdi A, Dalir Ghaffari A, Ghaffarifar F, Majidiani H. In silico evaluation of Toxoplasma gondii rhoptry neck proteins (TgRONs) for potential immunogenic epitopes. EXCLI J. 2025;24:749-73.
13. Foroutan M, Ghaffari AD, Ghaffarifar F, Karimipour-Saryazdi A, Birgani AA, Majidiani H, et al. In silico-based investigation of the immunogenicity and biochemical attributes of Toxoplasma gondii apical membrane antigen 1 (TgAMA1). J Parasitol Res. 2025;2025:3514414.
14. Ghaffari AD, Dalimi A, Ghaffarifar F, Pirestani M, Majidiani H. Immunoinformatic analysis of immunogenic B- and T-cell epitopes of MIC4 protein to designing a vaccine candidate against Toxoplasma gondii through an in-silico approach. Clin Exp Vaccine Res. 2021;10(1):59-77.
15. Rapin N, Lund O, Bernaschi M, Castiglione F. Computational immunology meets bioinformatics: the use of prediction tools for molecular binding in the simulation of the immune system. PLoS One. 2010;5(4):e9862.
16. Berzofsky JA. Immunogenicity and antigen structure. Fundamentai immunology, Third ed. 1993:235-82.
17. Lee TY, Hsu JB, Chang WC, Wang TY, Hsu PC, Huang HD. A comprehensive resource for integrating and displaying protein post-translational modifications. BMC Res Notes. 2009;2:111.
18. Yada RY, Jackman RL, Nakai S. Secondary structure prediction and determination of proteins-a review. Int J Pept Protein Res. 1988;31(1):98-108.
19. Berjanskii MV, Wishart DS. Application of the random coil index to studying protein flexibility. J Biomol NMR. 2008;40(1):31-48.
20. Carugo O, Djinovic-Carugo K. Half a century of Ramachandran plots. Acta Crystallogr D Biol Crystallogr. 2013;69(Pt 8):1333-41.
21. Khan IA, Moretto M. Immune responses to Toxoplasma gondii. Curr Opin Immunol. 2022;77:102226.
22. Sayles PC, Gibson GW, Johnson LL. B cells are essential for vaccination-induced resistance to virulent Toxoplasma gondii. Infect Immun. 2000;68(3):1026-33.
23. El-Kady IM. T-cell immunity in human chronic toxoplasmosis. J Egypt Soc Parasitol. 2011;41(1):17-28.
| Files | ||
| Issue | Vol 21 No 1 (2026) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v21i1.21639 | |
| Keywords | ||
| Toxoplasma gondii Bioinformatics In silico Microneme proteins Vaccine | ||
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