Design of a cross-protective multi-epitope vaccine targeting the most prevalent typhoidal and non-typhoidal Salmonella serovars

Salmonella Typhi, the bacteria causing typhoid, is a major health issue in developing and less developed countries. The existing typhoid conjugate vaccine (Vi-TCV) has its limitations, as it might encourage the rise of Vi antigen-negative strains, making the vaccine ineffective. There are also no approved vaccines for the non-typhoidal Salmonella serovars. A potential solution can be a vaccine made from parts of different proteins found on the surface of the bacteria. In this study, we first analyzed the whole proteome of S. Typhi and selected epitopes from four surface proteins such as peptidoglycan-associated lipoprotein, outer membrane protein S1, outer membrane protein F, and outer membrane porin L, as those were superior to the epitopes of some other surface proteins in terms of antigenicity, promiscuity to interact with MHC alleles, non-allergenicity, non-resemblance with human proteins, and conservation across different serovars and strains. Through different filters, we chose 7 CTL and 7 HTL epitopes along with 3 IFN-γ-inducing epitopes. These epitopes were combined using linkers and a suitable adjuvant, creating a multi-epitope vaccine consisting of 201 amino acids. This multi-epitope vaccine candidate showed promising results in molecular docking, molecular dynamics, and immune simulation. BLAST search revealed that the chosen epitopes for vaccine development against Salmonella Typhi are 100 % identical with corresponding epitopes of Salmonella Paratyphi A, Salmonella Typhimurium, and Salmonella Enteritidis, indicating that the proposed vaccine might give cross-protection against major Salmonella pathogenic serovars.