Molecular dynamics simulation of a novel multi-epitope vaccine design against Salmonella enterica paratyphi A using a computational approach.

Salmonella enterica serovar Paratyphi A is a significant pathogen responsible for enteric fever, particularly in developing countries, contributing to high morbidity and mortality. Current vaccines predominantly target S. Typhi, leaving a critical gap in protection against Paratyphi A strains. The absence of an effective vaccine for Paratyphi A is a significant public health concern, given its potential for outbreaks and long-term healthcare burdens. Designing a targeted vaccine is essential to reduce the incidence of enteric fever and improve global health outcomes. This study focuses on developing a multi-epitope mRNA-based vaccine against S. enterica Paratyphi A using in silico approaches, which can provide a rapid, cost-effective solution for vaccine development. A comprehensive in silico approach was utilized to design a multi-epitope vaccine candidate. Epitopes for major histocompatibility complex (MHC) Class I and II were predicted using the Immune Epitope Database (IEDB), with population coverage analysis conducted to evaluate potential efficacy across diverse populations. The selected epitopes were combined into a chimeric construct, followed by 3D modeling and molecular docking studies with Toll-like receptors (TLR4 and TLR6) using ClusPro. The stability and interaction dynamics of the vaccine-receptor complexes were further assessed through molecular dynamics (MD) simulations using the iMODS server. The population coverage analysis indicated that the vaccine epitopes provided 86.62% coverage for MHC Class I, 82% for MHC Class II, and an impressive 97% combined coverage. Docking studies revealed strong binding affinities, with interaction energy scores of -1418.2 and - 1446.1 for TLR4 and TLR6, respectively. MD simulations confirmed the stability of the vaccine-receptor complexes, with favorable interaction profiles and low energy levels, suggesting strong potential for immune activation. The computational results indicate strong antigenicity and immunogenicity, providing a foundation for further experimental validation of an effective preventive strategy against enteric fever.