In silico analysis and in vivo assessment of a novel epitope-based vaccine candidate against uropathogenic Escherichia coli

• Published in: Scientific reports 2020-10, Vol.10 (1), p.16258-16258, Article 16258
• Main Authors: Hasanzadeh, Sara, Habibi, Mehri, Shokrgozar, Mohammad Ali, Ahangari Cohan, Reza, Ahmadi, Khadijeh, Asadi Karam, Mohammad Reza, Bouzari, Saeid
• Format: Article
• Language: English
• Subjects: 631/250/590; 631/61/51; Animals; Antibiotics; Antigens; Bioinformatics; Computer Simulation; Cytokines - metabolism; E coli; Epitopes; Epitopes - immunology; Escherichia coli; Escherichia coli Infections - immunology; Escherichia coli Infections - prevention & control; Escherichia coli Vaccines - immunology; Escherichia coli Vaccines - therapeutic use; Fusion protein; Humanities and Social Sciences; Immunoglobulin A; Immunoglobulin G; Immunoglobulin G - immunology; Interferon; Lymphocytes T; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Molecular dynamics; Mucosa; multidisciplinary; Science; Science (multidisciplinary); TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Urinary tract; Urinary Tract Infections - immunology; Urinary Tract Infections - prevention & control; Urogenital system; Uropathogenic Escherichia coli - immunology; Vaccines; Virulence
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-73179-w

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.