Introduction: Streptococcus pneumoniae causes invasive and non-invasive diseases in children and adults. Currently, there are two types of pneumococcal vaccines: 23-valent pneumococcal polysaccharide vaccine and 13-valent pneumococcal conjugate vaccine which have caused many failures. Therefore, a new generation of pneumococcal vaccines is being pursued. Methods: An improved version of our previous study was performed using recombinant C-terminal of pneumococcal polyhistidine triad protein D (PhtD-C) as a vaccine antigen. The antigen was combined with meningococcal outer membrane vesicle (OMV) and alum as adjuvants to immunize BALB/c mice intraperitoneally. The generated total IgG, specific IgG, IgG1 and IgG2a antibodies and the killing ability of pneumococci by an opsonophagocytosis assay were then assayed. Results: Immunization by 30 µg PhtD-C and 50 µg OMV as an adjuvant, induced higher amounts of functional antibodies compared to our previous study while killing 50-55% of pneumococci cells. Conclusion: At optimized concentrations, PhtD-C and meningococcal OMV could be considered as a potent immunogens and the induced specific IgGs were effective and functional for killing pneumococci.
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 Bcell 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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