Designing a Multi-Epitope Vaccine Candidate against Salmonella Typhi Using Immunoinformatics Approach

Abstract

Salmonella enterica subsp. enterica serovar Typhi (Salmonella Typhi) is the causative agent of typhoid. A large population living in developing and under-developed countries are mainly susceptible to the infection of this pathogen. The use of an effective vaccine targeting the highest-risk populations could be an extremely useful approach in the prevention of typhoid. The currently licenced and widely used typhoid conjugate vaccine (Vi-TCV) can promote emergence of Vi antigen negative strains, necessitating the design of alternative vaccine candidates. Vaccine consisting of multiple epitopes from different surface proteins can serve as a solution to this problem. In this study, 10 Salmonella Typhi whole genome sequences were retrieved from NCBI database. From the proteomes of these organisms, epitopes from four surface proteins such as peptidoglycan-associated lipoprotein (Accession No. AYU85048.1), outer membrane protein S1 (Accession No. AYU86170.1), outer membrane protein F (Accession No. AYU85220.1 and outer membrane porin L (Accession No. AYU87629.1) returned better results than some other surface proteins in terms of antigenicity, promiscuity to interact with MHC alleles, non-allergenicity, non-similarity with human proteins, conservation and population coverage. These epitopes were joined together using suitable adjuvant and linkers, resulting in a vaccine candidate comprising 201 amino acids. This multi epitope vaccine candidate exhibited promising results in molecular docking, molecular dynamics simulation 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. The prospective results in this dry laboratory work demonstrates potential positive outcomes in the future for in vivo animal model testing and clinical analyses.