Reverse vaccinology approach to design a vaccine targeting membrane lipoproteins of <i>Salmonella typhi</i>

Typhoid fever caused by Salmonella is one of the major health issues worldwide, resulting in millions of cases and has very high rates of morbidities. The therapeutic approaches need to be updated for the effective elimination of the bacterial pathogen. The designing of the multiepitope vaccine against Salmonella using comparative proteomics and reverse vaccinology has covered up all the epitopes that induce sufficient immune responses in the host body. Out of the 4293 proteins, 15 outer membrane proteins have been selected based on their antigenicity, low transmembrane helix (<1), and virulence-associated factors. With the help of the reverse vaccinology approach, the epitopes of MHC Class I, Class II, and B-cell with antigenic, low toxicity, and that have the potential to generate immunogenic response have been identified. Based on the comparative analysis of all the epitopes, a multiepitope-based construct has been designed. Based on physicochemical properties and docking scores for HLA and TLR4, the VC5 construct has been selected, and the molecular dynamic simulation studies have confirmed their interaction. The dissociation constant of the VC5 and TLR4 was found to be 3.1 x 10-9. Different immune cell activation has been analyzed, representing the potentiality of the VC5 construct as an effective vaccine target. In silico cloning of VC5 in pET28a has also been performed, which requires experimental validation. Therefore, the present study designs a multi-epitope vaccine VC5 targeted to the membrane lipoproteins of Salmonella typhi.Communicated by Ramaswamy H. Sarma.