Shigellosis is a severe diarrheal disease with high mortality and morbidity rate. Until now, there is no approved vaccine against the disease. Therefore, the present study was planned to design a novel multi-epitope vaccine against Shigella spp., the causative agents of the disease based on the immunoinformatic tools. For this end, firstly seven conserved antigens of the bacteria, including IpaA, IpaB, IpaC, IpaD, OmpC, OmpF and VirG were selected. Then, linear B-cell epitope mapping of these proteins was carried out and top-ranked and shared epitopes were selected based on antigenicity, allergenicity, stability, toxicity and physicochemical properties for further analysis. In next step, B-cell derived T-cell e... More
Shigellosis is a severe diarrheal disease with high mortality and morbidity rate. Until now, there is no approved vaccine against the disease. Therefore, the present study was planned to design a novel multi-epitope vaccine against Shigella spp., the causative agents of the disease based on the immunoinformatic tools. For this end, firstly seven conserved antigens of the bacteria, including IpaA, IpaB, IpaC, IpaD, OmpC, OmpF and VirG were selected. Then, linear B-cell epitope mapping of these proteins was carried out and top-ranked and shared epitopes were selected based on antigenicity, allergenicity, stability, toxicity and physicochemical properties for further analysis. In next step, B-cell derived T-cell epitopes were determined and appropriate epitopes were selected for incorporation into the final construct. Moreover, the selected epitopes and two mucosal adjuvants including ctxB and LT-IIc were joined using appropriate linkers. The three dimensional structure of the final construct was modeled and evaluated in term of structural quality and presence of conformational B-cell epitopes. Furthermore, binding affinity of the proposed vaccine to MHC I and II molecules were evaluated through molecular docking method using Hex 8.0. as well as the stability of the vaccine-MHC complexes was monitored by molecular dynamics method using the NAMD graphical user interface embedded in visual molecular dynamics. Finally, to evaluate the immunogenicity of the designed protein, the protein was administered to BALB/c mice and the serum IgG was determined by ELISA. The results indicated that the proposed vaccine has high structural quality and binding affinity to both MHC I and II molecules. Moreover, molecular dynamics studies confirmed that the vaccine-MHC docked complexes were stable during simulation time. Animal study showed that the proposed protein is able to evoke mice's humoral immune response. In sum, the results suggested that the proposed candidate vaccine could be considered as a promising anti-shigellosis vaccine.,Copyright © 2019 Elsevier Ltd. All rights reserved.
