Abstract
Uropathogenic Escherichia coli (UPEC) are common pathogens in urinary tract infections (UTIs), which show resistance to antibiotics. Therefore, there is a need for a vaccine to reduce susceptibility to the infection. In the present study, bioinformatics approaches were employed to predict the best B and T-cell epitopes of UPEC virulence proteins to develop a multiepitope vaccine candidate against UPEC. Then, the efficacy of the candidate was studied with and without Freund adjuvant. Using bioinformatics methods, 3 epitope-rich domains of IutA and FimH antigens were selected to construct the fusion. Molecular docking and Molecular dynamics (MD) simulation were employed to investigate in silico interaction between designed vaccine and Toll-like receptor 4 (TLR4). Our results showed that the levels of IgG and IgA antibodies were improved in the serum and mucosal samples of the vaccinated mice, and the IgG responses were maintained for at least 6 months. The fusion protein was also able to enhance the level of cytokines IFN.γ (Th1), IL.4 (Th2), and IL.17. In challenge experiments, all vaccine combinations showed high potency in the protection of the urinary tract even after 6 months post first injection. The present study indicates that the designed candidate is able to evoke strong protective responses which warrant further studies.
Highlights
Uropathogenic Escherichia coli (UPEC) are common pathogens in urinary tract infections (UTIs), which show resistance to antibiotics
Urinary tract infections (UTIs) are one of the most common infections occurring both in the community and hospitals, affecting 150 million people each year worldwide
UTIs are caused by different kinds of pathogens, but most commonly by uropathogenic Escherichia coli (UPEC)[1,2]
Summary
According to the results shown, mice vaccinated with both fusion and fusion plus Freund could enhance the IgG levels in comparison with the control groups. According to the ELISA data, higher levels of IFN.γ, IL.[4], and IL.[17] cytokines were measured in supernatant of the splenocytes isolated from immunized groups as compared to control groups (p < 0.001) These findings showed that immunization with fusion plus Freund significantly increased the IFN.γ levels compared to the fusion protein alone (p < 0.001). As a result of the first challenge, the mice groups immunized with the fusion or the fusion plus Freund showed a significant reduction (102–103 folds) in bacterial loads in both bladder and kidney organs as compared to the control groups (p < 0.05) (Fig. 9A1,B1). The results of the challenge after 6 months indicated that the bacterial levels in the vaccinated groups were significantly reduced ( 102–103 folds) in the bladder (p < 0.01) and kidneys (p < 0.01) as compared to the control groups (Fig. 9A2,B2)
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