Afshari E, Ahangari Cohan R, Sotoodehnejadnematalahi F, Mousavi S F. In-silico Analysis of Pneumococcal Heat-Shock Protein (DnaJ) to Predict Novel Multi-Epitope Vaccine Candidates. vacres 2022; 9 (1) :11-33
URL:
http://vacres.pasteur.ac.ir/article-1-287-fa.html
چکیده: (1734 مشاهده)
Introduction: To prevent pneumococcal infections, especially meningitis and bacteremia, and to overcome the serotype-dependent limitation of polysaccharide-based vaccines, the development of conserved protein-based vaccines is essential. This study aimed at investigate the in-silico analysis and epitope mapping of pneumococcal DnaJ for the first time, and to design the multi-epitope based vaccines with different categories by focusing on induction of both humoral and cellular immunities. Methods: We predicted B- and T-cell epitopes, IL-4, IL-17, IL-10, and IFN-γ inducer epitopes of DnaJ using Immunoinformatics tools. The immunogenicity and conservation score of the predicted epitopes among pneumococcal prevalent clinical serotypes, the immune simulation of DnaJ administration in mammals and potential regions involved in DnaJ-TLRs interactions were analyzed. Finally, we proposed three classes of multi-epitope DnaJ-based vaccine candidates. Results: This protein had 24 and 15 predicted linear B-cell and helper T-cell epitopes, respectively, with a conservation score of 86-100% among prevalent clinical pneumococcal serotypes. DnaJ also had many IL-4 and IFN-γ inducing epitopes and was considered an IL-10 and IL-17 inducer protein. The immune simulation showed induction of both humoral and cellular immunity against DnaJ. The residues at positions 274, 280, 292, 297, 300, 316-319, 333, 336-340, 358, 363-366, and 372 were predicted to be involved in DnaJ-TLR2 and DnaJ-TLR4 interactions. Three classes of proposed DnaJ-based constructs were based on only B-cell epitopes, only helper T-cell epitopes, and multi-epitopes of B- and T-cell and IL-17 epitopes. Conclusion: The results showed that although DnaJ has been reported to play an important role in cellular immunity, our results indicated the high potential of DnaJ to stimulate mucosal, humoral, and cellular immunity.
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Vaccine technology دریافت: 1401/3/19