Vaccination with recombinant FimH fused with flagellin enhances cellular and humoral immunity against urinary tract infection in mice

Urinary tract infection (UTI) caused by Uropathogenic Escherichia coli (UPEC) is one of the most common infections in the world. Despite extensive efforts, a vaccine that confers protection against UTIs in human is currently lacking. In this study, the ability of flagellin (FliC), a Toll-like receptor 5 (TLR5) agonist of UPEC strain, and the conventional adjuvant Montanide ISA 206 to enhance the protective immune responses of FimH against urinary tract infection have been compared. Mice immunized with the fused FimH.FliC protein induced significantly higher humoral (IgG1 and IgG2a) and cellular (IFN-γ and IL-4) immune responses than with FimH alone or FimH admixed with FliC. The immune responses of Montanide formulations were comparable to that of the fusion protein and were significantly higher than that of FimH alone. Our results showed that based on the IgG1/IgG2a ratios, FliC directed the anti-FimH responses preferentially toward Th2 and Montanide toward Th1. The FimH.FliC fusion and FimH admixed with FliC and Montanide formulations gave the best results in protection of bladder colonization, compared to the control mice. The results propose new promising vaccine formulation based on the adjuvant properties of FliC and Montanide against UTI caused by UPEC strains.

► We describe the first UTI vaccine formulations based on the FliC or Montanide.
► FliC or Montanide induced strong humoral and cell immune responses.
► Based on the IgG1/IgG2a, FliC directed responses to Th2, and Montanide to Th1.
► FimH.FliC and FimH + FliC + Montanide significantly reduced bladder colonization.
► This study presents FimH.FliC as a promising vaccine candidate against UTI.