Determination of Effective Prophylactic Responses of Truncated Flagellin Protein as a Vaccine Candidate Against Uropathogenic Escherichia coli

Abstract

Uropathogenic Escherichia coli (UPEC) is a major cause of more than 80% of urinary tract infections (UTIs), a global health problem, and the second most common infectious disease. UTIs are responsible for approximately 40% of all nosocomial infections and 50% of all bacteremia. Since an approved vaccine against UTIs is not yet approved, evaluating different antigens, injection routes, and adjuvants is necessary to assess the ideal vaccines. In this study, we constructed a fusion protein composed of a truncated form of FimH antigen, the key virulence factor of UPEC, and the FliC antigen of Salmonella typhimurium as an adjuvant. After bioinformatics analysis, the fusion protein was cloned, expressed, and immunologically evaluated in mice. The bladder challenge assay was also used to examine the level of protection in the bladder and kidneys of the immunized mice. The levels of IgG and IgA antibodies in the serum and urine of mice vaccinated with the truncated FimH.FliC (tFimH.FliC) significantly increased compared to the FliC and PBS groups. The cytokine assay showed that tFimH.FliC fusion protein induced higher levels of IFN‐γ, IL‐4, and IL‐17 than the FimH and PBS groups. Additionally, the results of the challenge assay showed a significant decrease in the colony count of bacteria in all of the groups compared to the control group. Our findings showed that the designed candidate can develop effective prophylactic responses against UTIs caused by UPEC strains and that truncated FimH, without an unwanted domain, is an ideal vaccine target.