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

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.

Proteome Based Approach Defines Candidates for Designing a Multitope Vaccine against the Nipah Virus

“…The approach of predicting and designing vaccines through in silico studies has improved massively in the last few years, where its applications extended to involve bacteria, viruses, fungi, and even cancer [26]. Multitope vaccine has been pre-dicted through computational approaches against several microorganisms such as Mayaro virus [27], Lassa virus [28], COVID-19 [29], and E. coli [30], where the predicted vaccine of the last study was expressed and analyzed through wet lab experimental validation and showed protection against urinary tract infection caused by uropathogenic E. coli in animal models. The application of immunoinformatics for designing NiV vaccine through epitope prediction was shown in many studies.…”

Differences of virulence factors, and antimicrobial susceptibility according to phylogenetic group in uropathogenic Escherichia coli strains isolated from Korean patients

“…FyuA causes invasion of bacteria into the bloodstream from the urinary tract and is associated with highly pathogenic strains [ 19 , 42 ]. Various vaccines are being developed according to the mechanisms of virulence factors, mainly targeting adhesion molecules and iron metabolism [ 19 , 22 ]. Vaccines related to toxins have not yet achieved significant results [ 13 ].…”

“…Vaccines under development are targeting the virulence factors widely distributed in uropathogenic E. coli [ 16 , 18 – 21 ]. Most vaccines for uropathogenic E. coli primarily target adhesion molecules, iutA and fyuA [ 19 , 22 ]. E. coli can be categorized into four major groups, A, B1, B2, and D [ 23 ].…”

D-Mannoside FimH Inhibitors as Non-Antibiotic Alternatives for Uropathogenic Escherichia coli

“…The consensus sequences, without noise and formatting, were translated from nucleotides to amino acids, taking into account the percentage of identity for all isolates in a range of 97–100%. Hasanzadeh et al [ 35 ] confirm that the fimH sequence in UPEC strains maintains a 97% similarity percentage based on the results of the sequence homology of the fimH gene; thus, this urovirulent gene is associated with genetic variants and, therefore, could be clinically relevant. Nevertheless, it is known that the fimH gene is subjected to a strong selective pressure and it is likely to show a high degree of sequence heterogeneity contributing to a more precise characterization of the UPEC strains [ 36 ].…”