A heterologous prime-boost route of vaccination based on the truncated MrpH adhesin and adjuvant properties of the flagellin from Proteus mirabilis against urinary tract infections

Complicated urinary tract infections (UTIs) caused by Proteus mirabilis are among the most common disorders. An effective vaccine could reduce the prevalence of such infections and antibiotic resistance in society. In the present study, the immunogenicity and protective efficacy of different combinations of the MrpH adhesion and flagellin (FliC) of P. mirabilis was evaluated in a prime-boost strategy of vaccination. Applying the FliC as an adjuvant resulted in the stimulation of mixed Th1- and Th2-immune responses against the truncated form of MrpH with a shift toward Th1. Furthermore, flagellin could maintain the persistence of antibody responses for at least 22 weeks after the first vaccine dose. It was found that the MrpH, especially in the fusion form, could improve the serum antibody and cellular responses of FliC alone and this suggests the possible adjuvant role of MrpH. The fusion MrpH.FliC and the mixture of FliC with MrpH indicated the highest humoral and cellular responses; this could significantly reduce the load of bacteria in the bladder and kidneys as compared to the control mice. In this study, the adjuvant property of the recombinant flagellin of P. mirabilis was evaluated for the first time in a vaccine candidate against UTI. The flagellin-based vaccines could induce the protective responses through a combination of mucosal and systemic route of administration. Such data indicates that the vaccine combinations of FliC and MrpH from P. mirabilis in fusion and non-fusion forms could be promising candidates for elimination of P. mirabilis in the urinary tract.