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Development of a Chimeric Vaccine Candidate Based on Toxoplasma Gondii Major Surface Antigen 1 and Apicoplast Proteins Using Comprehensive Immunoinformatics Approaches Publisher Pubmed



Asghari A1 ; Shamsinia S2 ; Nourmohammadi H3, 10 ; Majidiani H3 ; Fatollahzadeh M4 ; Nemati T4 ; Irannejad H5, 6 ; Nouri HR7, 8 ; Ghasemi E9 ; Shams M3
Authors
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Authors Affiliations
  1. 1. Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  2. 2. Department of Medical Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  3. 3. Zoonotic Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran
  4. 4. Department of Parasitology and Mycology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  5. 5. Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
  6. 6. Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran
  7. 7. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  8. 8. Immunoregulation Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  9. 9. Department of Medical Parasitology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran
  10. 10. Department of Internal Medicine, Shahid Mostafa Khomeini Hospital, Ilam University of Medical Sciences, Ilam, Iran

Source: European Journal of Pharmaceutical Sciences Published:2021


Abstract

This study was aimed at designing and evaluation of a multimeric vaccine construct against Toxoplasma gondii via utilization of SAG1 along with apicoplast ribosomal proteins (S2, S5 and L11). Top-ranked MHC-I and MHC-II binding as well as shared, immunodominant linear B-cell epitopes were predicted and joined together via appropriate linkers. Also, TLR-4 agonist (RS-09 synthetic protein) and His-tag were added to the N- and C-terminal of the vaccine sequence. The finally-engineered chimeric vaccine had a length of 291 amino acids with a molecular weight of 31.46 kDa. Physico-chemical features showed a soluble, highly-antigenic and non-allergenic candidate. Secondary and tertiary structures were predicted, and subsequent analyses confirmed the construct stability that was capable to properly interact with human TLR-4. Immunoinformatics-based simulation displayed potent stimulation of T- and B-cell mediated immune responses upon vaccination with the proposed multi-epitope candidate. In conclusion, obtained information demonstrated a highly antigenic vaccine candidate, which could develop high levels of IFN-γ and other components of cellular immune profile, and can be directed for toxoplasmosis prophylactic purposes. © 2021 Elsevier B.V.
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