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These diseases cause a significant amount of morbidity and mortality. Although polysaccharide vaccines are available, the protection provided by these vaccines is serotype\u2010dependent 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\u2010epitope vaccine against <jats:styled-content style=\"fixed-case\"><jats:italic>Streptococcus pneumoniae<\/jats:italic><\/jats:styled-content> 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\u2010cell, cytotoxic T cell and helper T cell epitopes were evaluated with linker and \u03b2\u2010defensin 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\u20104 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 IgG<jats:sub>1<\/jats:sub>\u2009+\u2009IgG<jats:sub>2<\/jats:sub> counts per mL. Similarly, cell\u2010mediated immunity was also enhanced by the designed vaccine construct. The construct was codon\u2010optimised and cloned in silico for expression in <jats:styled-content style=\"fixed-case\"><jats:italic>Escherichia coli<\/jats:italic><\/jats:styled-content>. 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