In silico design of a novel multi-peptide vaccine candidate against pneumococcal surface protein A (PspA) families ۱ and ۲

BACKGROUND AND OBJECTIVESStreptococcus pneumoniae has remained a leading cause of fatal infections such as pneumonia, meningitis and sepsis. High morbidity and mortality are the main concern for pneumococcal vaccine development. Due to the limitations of currently marketed polysaccharide-based vaccines, non-serotype-specific protein-based vaccines have received wide research interest in recent years. One step further is to identify high antigenic regions within highly-conserved proteins in order to develop peptide vaccines, providing broader serotype coverage and more effective protection. Pneumococcal surface protein A (PspA), a highly immunogenic surface protein produced by almost all pneumococcal strains, can elicit protective immunity against fatal pneumococcal infection.MATERIALS AND METHODSIn this study, immunoinformatics tools were used to design an effective multi-peptide vaccine based on PspA protein (families ۱ and ۲) against multiple strains of pneumococcus. The high-scoring B- and T-cell epitopes overlapping with each other shared between different servers were considered, and the final peptides from PspA families ۱&۲ were selected and merged together with suitable linkers. The prediction of physicochemical properties, antigenicity, allergenicity, toxicity, ۳D-structure, and conformational B cell epitopes in final construct, as well as molecular docking of final construct with HLA receptor and immune simulation were carried out using computational tools.RESULTS AND DISCUSSIONThe evaluation of the properties showed that final construct was soluble, antigenic, and non- allergenic. Furthermore, the protein was found to be acidic and hydrophilic in nature. The ۳D- structure was built and refined, and the Ramachandran plot, ProSA–web, and ERRAT validated the quality of final model. Molecular docking analysis showed that the designed construct could interact strongly with HLA. Finally, codon optimization was performed for gene expression in E. coli, followed by in silico cloning in the pET۲۸a(+) vector. The computational analysis showed that the final construct passed the evaluations with satisfactory scores and had potential to elicit robust immune responses.CONCLUSIONFor the first time this study presents a novel vaccine containing of the immunodominant regions of PspA antigens. The in silico analysis revealed acceptable results, however, the suggested vaccine needs to be experimentally confirmed in laboratory to ensure its safety and immunogenicity