Designing self-assembled peptide nanovaccine against Streptococcus pneumoniae: An in silico strategy. (December 2019)

• Record Type: Journal Article
• Authors: Dorosti, Hesam; Eslami, Mahboobeh; Nezafat, Navid; Fadaei, Fardin; Ghasemi, Younes
• Is Part Of: Molecular and cellular probes. Volume 48(2019)
• Publication Date: 2019-12
• Subjects: Streptococcus pneumoniae -- Epitope -- Nanovaccine -- Structural evaluation -- Immunoinformatics; Molecular probes -- Diagnostic use -- Periodicals; Pathology, Cellular -- Technique -- Periodicals; Cell Biology -- Periodicals; Molecular Biology -- Periodicals; Sondes moléculaires -- Utilisation diagnostique -- Périodiques; Cytopathologie -- Technique -- Périodiques; 572
• DOI: 10.1016/j.mcp.2019.101446
• Languages: English
• ISSNs: 0890-8508

Abstract

Abstract: Streptococcus pneumoniae is the main cause of diseases such as meningitis, pneumoniae and sepsis, especially in children and old people. Due to costly antibiotic treatment, and increasing resistance of pneumococcus, developing high-efficient protective vaccine against this pathogen is an urgent need. Although the pneumoniae polysaccharide vaccine (PPV) and pneumonia conjugate vaccines (PCV) are the efficient pneumococcal vaccine in children and adult groups, but the serotype replacement of S. pneumoniae strains causes the reduction in efficacy of such vaccines. For overcoming the aforesaid drawbacks epitope-based vaccines are introduced as the relevant alternative. In our previous research, the epitope vaccine was designed based on immunodominant epitopes from PspA, CbpA antigens as cellular stimulants and PhtD, PiuA as humoral stimulants. Because the low immunogenicity is the main disadvantage of epitope vaccine, in the current study, we applied coiled-coil self-assembled structures for developing our vaccine. Recently, self-assembled peptide nanoparticles (SAPNs) have gained much attention in the field of vaccine development due to their multivalency, self-adjuvanticity, biocompatibility, and size similarity to pathogen. In this regard, the final designed vaccine is comprised of cytotoxic T lymphocytes (CTL) epitopes from PspA and CbpA, helper T lymphocytes (HTL) epitopes from PhtD and PiuA, the pentamer and trimmer oligomeric domains form 5-stranded and 3-stranded coiled-coils as self-assembled scaffold, Diphtheria toxoids (DTD) as a universal T-helper, which fused to each other with appropriate linkers. The four different arrangements based on the order of above-mentioned compartments were constructed, and each of them were modeled, and validated to find the 3D structure. The structural, physicochemical, and immunoinformatics analyses of final vaccine construct represented that our vaccine could stimulate potent immune response against S. pneumoniae ; however, the potency of that should be approved via various in vivo and in vitro immunological tests. Highlights: Stimulating cellular and especially humoral immunities are essential for protection against Streptococcus Pneumoniae. Immunodominant epitopes were selected from highly protective antigens of S. pneumoniae : PspA, CbpA, PiuA, PhtD. In order to bypass the low immunogenicity of epitope-based peptide vaccine the self-assembled motifs, coiled-coil structure, was applied as the vaccine scaffold. The structural, physicochemical, and immunoinformatics results indicate that the designed vaccine can incite strong immune response against S. pneumoniae.