Immunoinformatics aided design of a novel epitope-based vaccine candidate against pneumococcal surface adhesion A (PsaA)
Immunoinformatics aided design of a novel epitope-based vaccine candidate against pneumococcal surface adhesion A (PsaA)
Mona Shafaghi,1Zohreh Bahadori,2,*
1. 1 Department of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran. 2 Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran. 2. 1 Department of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran. 2 Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran.
Introduction: Streptococcus pneumoniae (pneumococcus) cause life-threatening bacterial infections such as meningitis, sepsis, and pneumonia if it invades sterile regions of the body. Moreover, pneumococcus is one of the leading causes of severe secondary infections following viral respiratory diseases such as coronavirus. Because of the boundaries of available S. pneumoniae vaccines, the development of a powerful, broad-spectrum, and cost-effective vaccine that can be effective in preventing infections caused via different pneumococcal serotypes is a significant concern of World Health Organization. Protein-based vaccine, comprising conserved pneumococcal protein antigen, can give an alternative to serotype-dependent vaccines. Pneumococcal surface adhesion A (PsaA), a highly conserved and immunogenic surface protein, can produce different levels of protection against immunological challenges with numerous pneumococcal serotypes.
Methods: In this study, the PsaA protein was considered to predict B and helper T cell epitopes using immunoinformatics tools. The immunodominant regions were selected and joined with the appropriate linker to build the final construct. Evaluation of physicochemical, antigenic and toxicity characteristics, prediction of 3D model and structural B cell epitopes in the final model, molecular docking of the engineered construct with HLA receptor and immune response simulation were performed by computational tools.
Results: In silico outcomes indicated that the designed construct is stable, soluble, antigenic, and non-toxic. The 3D model was constructed and refined, and Ramachandran plot, ProSA Z-score and ERRAT confirmed the quality of 3D-model. Docking analysis showed favorable interactions between HLA and the developed construct. Finally, codon optimization was performed to enhance the expression of the vaccine in E. coli followed by in silico cloning in pET28a(+) plasmid. Computational results demoneatrated that the proposed vaccine could pass the evaluations with satisfactory scores and was considered to have the potential to generate strong immune responses.
Conclusion: For the first time, this work provides a new vaccine containing the dominant epitopic regions of the PsaA antigen. Computational analysis showed valid results, however, in vitro and in vivo experiments should be performed to prove the potency of the vaccine candidate.
Keywords: Pneumococcal surface adhesion A (PsaA), Epitope-based vaccine candidate, Immunoinformatics.