Multiepitope-based vaccine design against DiiA inStreptococcus pneumoniae, An immunoinformatics approach

Abstract

AbstractStreptococcus pneumoniae(SPN) infection has resulted in significant morbidity and mortality worldwide in children and adults. It is responsible for colonizing the human nasopharynx and can also cause diseases, including otitis media, pneumonia, bacteraemia, and meningitis. SPN is exhibiting resistance to multiple antibiotics and current vaccines have a number of limitations including poor immunogenicity and limited effectiveness against all pneumococcal serotypes. Here, we explain the design of a novel multi-epitope vaccine using Dimorphic invasion-involved protein A (DiiA) as a target protein. For designing the vaccine, the sequence of DiiA was obtained and various bioinformatics tools were employed to predict multiple CTL, HTL, B lymphocyte epitopes of DiiA. After evaluating antigenicity, allergenicity, toxicity, and immunogenicity, the most promising epitopes were chosen for constructing the vaccine, followed by an analysis of their physicochemical and immunological characteristics.The prediction, refinement, and validation of the 3D structure of the vaccine were carried out. Molecular docking, molecular dynamic simulation, and immune simulation were executed to examine the binding affinities and biological interactions at the atomic level between the vaccine and Toll-like receptor (TLR4). Vaccine translation, codon optimization were performed and expression efficiency was assessed through an in-silico cloning experiment performed to transfer into pET28a(+) plasmid vector.The obtained results proved that the vaccine maintained structural stability and possessed the capability to stimulate an efficient immune response againstS. pneumoniaeinfection. The constructed vaccine has the potential for subsequent wet lab experimentation, leading to the development of an innovative vaccine.