en Reverse vaccinology Reverse vaccinology Original article Original article <span style="font-size:10pt"><span style="tab-stops:62.4pt"><span new="" roman="" style="font-family:" times=""><b><span style="letter-spacing:-.1pt">Introduction: </span></b><span style="letter-spacing:-.1pt">The most widespread gastrointestinal infection globally is attributed to non-typhoidal <i>Salmonella</i> (NTS). Given the rising prevalence of antibiotic-resistant strains and the absence of commercially available vaccines, there is a crucial need for research and development of new vaccines against NTS.</span> <span style="letter-spacing:-.1pt">The purpose of the present study was to design a multi-epitope vaccine targeting non-typhoidal&nbsp;<i>salmonella</i>&nbsp;serovars (<i>Salmonella</i>&nbsp;<i>typhimurium</i> and&nbsp;<i>Salmonella</i>&nbsp;<i>enteritidis</i>) based on fimbriae protein using an immunoinformatics approach. <b>Methods:</b> The sequences of the fimbriae protein were obtained and the predicted epitopes for B and T lymphocytes were identified. The epitopes&#39; antigenic features, non-allergenicity, and non-toxicity were investigated, and the vaccine model was constructed. The characteristics of the vaccine were determined, and its effectiveness was evaluated through docking, molecular dynamics simulation involving the interaction between the vaccine and immune receptors, and immunological simulation. The vaccine was then optimized for cloning. <b>Results:</b> B and T lymphocyte-targeting vaccine construct was developed by selecting twelve epitopes. Immunoinformatics analyses predicted that the constructed vaccine is reliable and safe, hydrophilic, and exhibits stability under diverse temperatures and conditions. Additionally, it displayed the capability to bind to immune receptors TLR4, HLA-C, and HLA-DRB1. Moreover, this vaccine candidate stimulates antibody response and memory B and T cell activation after repeated injection. <b>Conclusion:</b> This study introduced the primary results of a novel multi-epitope vaccine against NTS based on adhesion protein.&nbsp; <i>In-silico</i> methods predicted that the proposed vaccine can potentially elicit an immune response and be expressed in the prokaryotic system</span></span></span></span> Non-typhoidal Salmonella, Fimbriae, Immunoinformatics, Multi-epitope vaccine 23 33 http://vacres.pasteur.ac.ir/browse.php?a_code=A-10-7831-1&slc_lang=en&sid=1 Babak Beikzadeh b.beikzadeh@bio.ui.ac.ir 0000-0001-7131-9949 Yes Assistant professor, Department of Cell and Molecular Biology & Microbiology,Faculty of Biological Sciences and Technology, University of Isfahan, Isfahan, Iran. Shahrzad Ahangarzadeh shahrzadahangar@yahoo.com No Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.