Computer Integrated Dominant Epitopes Evoke Protective Immune Response Against Streptococcus pneumoniae

Abstract

Streptococcus pneumoniae is a gram-positive bacterium responsible for various diseases like pneumonia, acute otitis media, sinusitis, meningitis and bacteraemia. These diseases cause a significant amount of morbidity and mortality. Although polysaccharide vaccines are available, the protection provided by these vaccines is serotype-dependent and not enough in sensitive populations like children and older people. Designing a subunit vaccine by using proteins that are responsible for the pathogenesis of diseases can provide better protection against bacterial infections. In this study, we present the design of a novel multi-epitope vaccine against Streptococcus pneumoniae using an immunoinformatic approach. More than 1170 epitopes were identified against B cells, cytotoxic T lymphocytes and helper T lymphocytes from more than 60 pneumococcal proteins. Epitopes were further screened, and potential epitopes were selected for vaccine development. Seven different vaccine combinations that harbour the 15 dominant B-cell, cytotoxic T cell and helper T cell epitopes were evaluated with linker and β-defensin adjuvant to finalise the best vaccine construct. Bioinformatics tools were used to analyse the construct's physicochemical properties, secondary and tertiary structures, allergenicity, antigenicity and immunogenicity. Docking studies with the TLR-4 receptor and molecular dynamics simulations indicated strong binding affinity and stability. In silico immune response simulations predicted robust IgG immune response generation and observed more than 200 000 IgG1 + IgG2 counts per mL. Similarly, cell-mediated immunity was also enhanced by the designed vaccine construct. The construct was codon-optimised and cloned in silico for expression in Escherichia coli. These findings suggest that the construct is a promising candidate for further experimental validation. © 2025 John Wiley & Sons Ltd.