Innovative approaches in pneumococcal vaccine development: Harnessing natural compounds and advanced delivery systems

Streptococcus pneumoniae is a leading cause of upper respiratory diseases worldwide, particularly in vulnerable populations such as young children, the aged, and immunosuppressed individuals. Although current pneumococcal vaccines have significantly reduced the global disease burden, limitations such as serotype replacement, variable immunogenicity, and accessibility challenges highlight the need for innovative approaches. This review explores strategies in pneumococcal vaccine development, the potential of protein-based vaccines that target conserved antigens, and recombinant technologies such as reverse vaccinology. The role of natural compounds, including bioactive molecules from Pleurotus ostreatus and saponin-based adjuvants, is discussed for their immunomodulatory properties. Advanced delivery systems like ISCOMATRIX and nanoparticle-based platforms are presented as solutions for enhancing mucosal and systemic immunity. This review further highlights the importance of integrating emerging technologies to ensure global accessibility. These innovations hold promise for developing universal and adaptable pneumococcal vaccines that are both effective and affordable for diverse populations.