Engineering a novel multi-epitope mRNA vaccine against major bacterial meningitis pathogens: E. coli K1, group B Streptococcus, Listeria monocytogenes, Neisseria meningitidis, and Streptococcus pneumoniae.

Bacterial meningitis poses a persistent global health threat, underscoring the need for innovative preventive strategies. This study details the computational design of a novel multi-epitope mRNA vaccine targeting outer membrane porins (OMPs), crucial virulence factors, from five primary causative pathogens: Escherichia coli K1, Group B Streptococcus, Listeria monocytogenes, Neisseria meningitidis, and Streptococcus pneumoniae. Employing a comprehensive in silico approach, we identified promising cytotoxic T-lymphocyte (CTL), B-cell, and helper T-lymphocyte (HTL) epitopes derived from these OMPs. Rigorous screening protocols were implemented to select epitopes exhibiting high antigenicity while minimizing potential allergenicity, toxicity, and autoimmunity. Molecular docking studies with corresponding MHC alleles predicted strong binding affinities and estimated potential global population coverage for the vaccine construct. Further in silico validation involved immune simulations and molecular dynamics analyses of the designed vaccine construct docked with Toll-like receptors 3 and 4 (TLR-3 and TLR-4), which confirmed the stability of the binding complex. These comprehensive computational analyses suggest that the designed multi-epitope mRNA vaccine holds considerable promise as a prophylactic intervention against bacterial meningitis and warrants further investigation through in vitro and in vivo experimental studies.