Journal Article10.34172/bi.2023.27513
Design and computational analysis of an effective multi-epitope vaccine candidate using subunit B of cholera toxin as a build-in adjuvant against urinary tract infections
Maryam Rezaei,Mehri Habibi,Parasoo Ehsani,Mohammad Reza Asadi Karam,Saeid Bouzari +4 more
TL;DR: The results of this study suggest that the designed vaccine protein could be a promising vaccine candidate against UTI, but further in vitro and in vivo studies are needed.
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Abstract: Introduction: Urinary tract infection (UTI) is one of the most common infections, usually caused by uropathogenic Escherichia coli (UPEC). However, antibiotics are a usual treatment for UTIs; because of increasing antibiotic-resistant strains, vaccination can be beneficial in controlling UTIs. Using immunoinformatics techniques is an effective and rapid way for vaccine development. Methods: Three conserved protective antigens (FdeC, Hma, and UpaB) were selected to develop a novel multi-epitope vaccine consisting of subunit B of cholera toxin (CTB) as a mucosal build-in adjuvant to enhance the immune responses. Epitopes-predicted B and T cells and suitable linkers were used to separate them and effectively increase the vaccine's immunogenicity. The vaccine protein's primary, secondary, and tertiary structures were evaluated, and the best 3D model was selected. Since CTB is the TLR2 ligand, molecular docking was made between the vaccine protein and TLR2. Molecular dynamic (MD) simulation was employed to evaluate the stability of the vaccine protein-TLR2 complex. The vaccine construct was subjected to in silico cloning. Results: The designed vaccine protein has multiple properties in the analysis. The HADDOCK outcomes show an excellent interaction between vaccine protein and TLR2. The MD results confirm the stability of the vaccine protein- TLR2 complex during the simulation. In silico cloning verified the expression efficiency of our vaccine protein. Conclusion: The results of this study suggest that our designed vaccine protein could be a promising vaccine candidate against UTI, but further in vitro and in vivo studies are needed.
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Figures
Fig. 1. (A) The sequence of vaccine-protein candidates based on epitope orders and CTB placement. The epitopes of Hma, UpaB, and FdeC antigens are shown in blue, grey, and yellow, respectively. All the linkers are colored in green, and CTB (build-in adjuvant) is shown in pink. (B) Representation of the 3D structure of the vaccine protein with PyMol. The respective elements، such as the loops, are given in green; the helices are in red, while the beta-sheets are colored in yellow. (C) Ramachandran plot of the vaccine protein: 85.07% of the residues are in the favored region, 3.08%of the residues are in the allowed, and only 1.49%residuesare in the outlier region. (D) ProSA plot of the vaccine protein. The Z-score is shown in a large black dot. The Z-score represents the overall quality of the model. 
Fig. 2. A docked complex of vaccine protein and TLR2. Vaccine protein is shown in green color, and TLR2 is shown in cyan color. The 3D structure of the docked complex of vaccine protein and TLR2 is visualized with PyMol. 
Table 4. Interacting amino acids of Vaccine protein-TLR2 by LigPlot+ software 
Table 3. Docking result of the vaccine protein and TLR2 by HADDOCK server 
Fig. 3. Predict the secondary structure of the designed vaccine. 
Fig. 7. C-ImmSim presentation of an in silico immune simulation with the designed vaccine protein. (A, B, C, D) the graphs show the population of B cells, T helper cells, T cytotoxic cells, and Dendritic cells, respectively. (E) Antibodies production after injection of vaccine protein is shown (the black vertical lines are antigen). (F) Graph displaying cytokines levels after administration of vaccine protein.
Citations
In-Silico Design and Immunoinformatics Analysis of a Multi-Epitope Vaccine Constructs, Based on Salmonella Pathogenesis Factors, for Use in Broiler Veterinary Medicine
Yuliana I. Mora-Ochoa,Lenin Ramirez Cando +1 more
- 01 Jan 2024
In-silico design and immunoinformatics analysis of a multi-epitope vaccine constructs, based on Salmonella pathogenesis factors, for use in broiler veterinary medicine.
Yuliana I. Mora-Ochoa,Lenin J Ramirez-Cando +1 more
TL;DR: This study designs a multi-epitope vaccine targeting Salmonella Typhimurium's fimH protein, using in-silico methods, incorporating adjuvants and modeling structures with advanced bioinformatics tools, demonstrating promising antigenicity, immunogenicity, and stability profiles for effective salmonellosis control in poultry.
References
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TL;DR: These analyses indicate that the suggested vaccine may produce particular immune responses against H. pylori, but laboratory validation is needed to verify the safety and immunogenicity status of the proposed vaccine design.
Evaluation of the effect of MPL and delivery route on immunogenicity and protectivity of different formulations of FimH and MrpH from uropathogenic Escherichia coli and Proteus mirabilis in a UTI mouse model
TL;DR: FimH fusion with MPL administered subcutaneously or intranasally could be a promising vaccine candidate for elimination of UTIs caused by UPEC and P. mirabilis.