همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

In Silico Design of a Chimeric Protein-Based Vaccine Against Salmonella Typhi: A Bioinformatics and Immunoinformatics Approach

نویسندگان :

Seyed Alireza Khoshuie-Esfahani¹ Neda Soleimani² Mohammad Yaghoubi-Avini³ Mohsen Bidar Ajerloo⁴

1- دانشگاه شهید بهشتی 2- دانشگاه شهید بهشتی 3- دانشگاه شهید بهشتی 4- دانشگاه جامع امام حسین (ع)

کلمات کلیدی :

Salmonella Typhi،Multi-epitope vaccine،Reverse vaccinology،Chimeric protein،Immune system simulation

چکیده :

Salmonella is a Gram-negative, rod-shaped bacterium from the family Enterobacteriaceae. This bacterium is a facultative anaerobe and an intracellular pathogen (Chong et al., 2021). Serovar Typhi causes human typhoid fever that leads to systemic infection in the host. This disease occurs exclusively in humans, whereas other strains like Salmonella Typhimurium are zoonotic and cause human gastroenteritis (Crump and Mintz, 2010). According to reports, approximately 200,000 deaths occur annually out of nearly 20 million typhoid fever cases worldwide. Contaminated water and food are the main factors contributing to the spread of this disease. Generally, underdeveloped regions experience a higher prevalence due to a lack of access to clean drinking water compared to developed areas (Dougan and Baker, 2014). This disease is treated using broad-spectrum antibiotics such as fluoroquinolones, cephalosporins, and ampicillin. However, the emergence of multidrug-resistant (MDR) bacteria has highlighted the urgent need for developing antibiotic-independent therapeutic approaches and prevention strategies through vaccines (Dyson et al., 2019). Since S. Typhi is an intracellular pathogen, the designed vaccine must effectively activate cell-mediated immunity in the host. Due to their peptide nature, Chimeric proteins are well-suited for eliciting cell-mediated immunity, resulting in adequate immunogenicity against S. Typhi (Chauhan and Khasa, 2023). Two antigens, T2942 and FliC, were selected as candidates for the design of a vaccine with these characteristics, among other antigens present in S. Typhi (Bumann, 2014). T2942 or StiV belongs to the outer membrane proteins (OMPs) category, which plays an independent role from the Type 3 Secretion System (T3SS) in the bacterium's attachment to intestinal epithelial cells and subsequent entry (Chowdhury et al., 2015). FliC is an acidic protein that encodes the flagellar protein in S. Typhi and is a mediator of epithelial activation. The protein sequences of these proteins were connected using a rigid linker and subjected to detailed bioinformatics and immunoinformatic analyses (Ghorbani et al., 2021). Phyre2 predicted the three-dimensional structure, and SAVES evaluated biophysical and biochemical parameters. According to the Ramachandran plot, 91.1% of residues are in the most favored region residues, and IUPred2A showed structural abnormalities. After confirming the bioinformatics parameters of the chimeric protein, immunoinformatic evaluations were performed. The protein's immunogenicity and non-allergenic properties were assessed. Bcepred and CBTOPE identified Linear and conformational B-cell epitopes, and T-cell epitope predictions indicated suitable binding to MHC molecules. The results from these analyses demonstrate the stability of the chimeric protein and its ability to elicit an immune response in the host. Detailed documentation for each will be presented in separate tables and charts. The designed chimeric protein, combining T2942 and FliC antigens, demonstrates promising immunogenic potential and structural stability, making it a viable candidate for a vaccine against Salmonella Typhi, with the capacity to effectively activate cell-mediated immunity in hosts.