A therapeutic epitopes-based vaccine engineering against Salmonella enterica XDR strains for typhoid fever: a Pan-vaccinomics approach.

Abstract

A prevalent food-borne pathogen, Salmonella enterica serotypes Typhi, is responsible for gastrointestinal and systemic infections globally. Salmonella vaccines are the most effective, however, producing a broad-spectrum vaccine remains challenging due to Salmonella's many serotypes. Efforts are urgently required to develop a novel vaccine candidate that can tackle all S. Typhi strains because of their high resistance to multiple kinds of antibiotics (particularly the XDR H58 strain). In this work, we used a computational pangenome-based vaccine design technique on all available (n = 119) S. Typhi reference genomes and identified one TonB-dependent siderophore receptor (WP_001034967.1) as highly conserved and prospective vaccine candidates from the predicted core genome (n = 3,351). The applied pan-proteomics and Immunoinformatic approaches help in the identification of four epitopes that may trigger adequate host body immune responses. Furthermore, the proposed vaccine ensemble demonstrates a stable binding conformation with the examined immunological receptor (HLAs and TRL2/4) and has large interaction energy determined via molecular docking and molecular dynamics simulation techniques. Eventually, an expression vector for the Escherichia. coli K12 strain was constructed from the vaccine sequence. Additional analysis revealed that the vaccine may help to elicit strong immune responses for typhoid infections, however, experimental analysis is required to verify the vaccine's effectiveness based on these results. Moreover, the applied computer-assisted vaccine design may considerably decrease vaccine development costs and speed up the process. The study's findings are intriguing, but they must be evaluated in the experimental labs to confirm the developed vaccine's biological efficiency against XDR S. Typhi.Communicated by Ramaswamy H. Sarma.