Evaluation of the effect of MPL and delivery route on immunogenicity and protectivity of different formulations of FimH and MrpH from uropathogenic Escherichia coli and Proteus mirabilis in a UTI mouse model

Habibi, Mehri; Karam, Mohammad Reza Asadi; Bouzari, Saeid

doi:10.1016/j.intimp.2015.05.027

Cited by 16 publications

(6 citation statements)

References 54 publications

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“…Intramuscular and subcutaneous routes of vaccination may be less effective because homing receptors are not expressed on B cells that are activated in peripheral lymph nodes (68). However, it has been shown that subcutaneous immunization performed with two weeks between boosts can significantly reduce kidney colonization and generate serum IgG in Balb/c mice when formulated with MPLA-FimH/MrpH (69), alum-FyuA (18) and adjuvant-IroN (17).…”

Section: Discussionmentioning

confidence: 99%

Optimization of an Experimental Vaccine to PreventEscherichia coliUrinary Tract Infection

Forsyth

Himpsl

Smith

et al. 2020

Preprint

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AbstractUrinary tract infections (UTI) affect half of all women at least once during their lifetime. The rise in extended-spectrum beta-lactamase-producing strains and potential for carbapenem resistance within uropathogenic Escherichia coli (UPEC), the most common causative agent of UTIs, creates an urgent need for vaccine development. Intranasal immunization of mice with UPEC outer membrane iron receptors, FyuA, Hma, IreA, or IutA, conjugated to cholera toxin, provides protection in the bladder or kidneys when challenged with UPEC CFT073 or 536. Based on these data, we sought to optimize the vaccination route (intramuscular, intranasal, or subcutaneous) in combination with adjuvants suitable for human use including alum, monophosphoryl lipid A (MPLA), unmethylated CpG synthetic oligodeoxynucleotides (CpG), polyinosinic:polycytodylic acid (polyIC), and mutated heat-labile E. coli enterotoxin (dmLT). Mice intranasally vaccinated with dmLT-IutA or dmLT-Hma displayed a significant reduction in bladder colonization (86-fold and 32-fold, respectively) with 40–42% of mice having no detectable colony forming units (CFU). Intranasal vaccination of mice with CpG-IutA and polyIC-IutA significantly reduced kidney colonization (131-fold) and urine CFU (22-fold), respectively. dmLT generated the most consistently robust antibody response in intranasally immunized mice, while MPLA and alum produced greater concentrations of antigen-specific serum IgG with intramuscular immunization. Based on these results, we conclude that intranasal administration of Hma or IutA formulated with dmLT adjuvant provides the greatest protection from UPEC UTI. This study advances our progress toward a vaccine against uncomplicated UTI, which will significantly improve the quality of life for women burdened by recurrent UTI and enable better antibiotic stewardship.ImportanceUrinary tract infections (UTI) are among the most common bacterial infection in humans, affecting half of all women at least once during their lifetimes. The rise in antibiotic resistance and health care costs emphasizes the need to develop a vaccine against the most common UTI pathogen, Escherichia coli. Vaccinating mice intranasally with a detoxified heat-labile enterotoxin and two surface exposed receptors, Hma or IutA, significantly reduced bacterial burden in the bladder. This work highlights progress in the development of a UTI vaccine formulated with adjuvants suitable for human use and antigens that encode outer membrane iron receptors required for infection in the iron-limited urinary tract.

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Section: Discussionmentioning

confidence: 99%

Optimization of an Experimental Vaccine to PreventEscherichia coliUrinary Tract Infection

Forsyth

Himpsl

Smith

et al. 2020

Preprint

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“…We recently reported the efficacy of MrpH.FimH fusion protein for vaccination against UTI that could protect immunized mice of challenge with an UPEC and P. mirabilis isolate . Previous studies have shown that FimH, the adhesin portion of type 1 fimbria of UPEC, is a novel TLR‐4 ligand enable to both stimulate the innate immune response and elicit protective immune responses against several infections .…”

Section: Discussionmentioning

confidence: 99%

“…The effective responses, including induction of cytokines and chemokine production as well as initiation of antimicrobial activities such as prevention of bacterial invasion into the bladder cells and eliciting bacterial expulsion from infected bladder cells (11,27). We recently reported the efficacy of MrpH.FimH fusion protein for vaccination against UTI that could protect immunized mice of challenge with an UPEC and P. mirabilis isolate (18,19). Previous studies have shown that FimH, the adhesin portion of type 1 fimbria of UPEC, is a novel TLR-4 ligand enable to both stimulate the innate immune response and elicit protective immune responses against several infections (14,15).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we constructed the MrpH.FimH fusion protein consisting of FimH from UPEC and MrpH adhesin of P. mirabilis as a new vaccine candidate against UTI. The intranasal and subcutaneous immunization of mice with the fusion protein in the absence of monophosphoryl lipid A (MPL) adjuvant resulting in the higher immunogenicity and protection compared with the FimH and MrpH alone or the mixture of the proteins . The results were interesting and we speculated that FimH antigen could have an adjuvant effect in these vaccine combinations.…”

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confidence: 99%

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Transurethral instillation with fusion protein MrpH.FimH induces protective innate immune responses against uropathogenic Escherichia coli and Proteus mirabilis

Habibi

Karam

Bouzari

2016

APMIS

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Urinary tract infections (UTIs) are among the most common infections in human. Innate immunity recognizes pathogen-associated molecular patterns (PAMPs) by Toll-like receptors (TLRs) to activate responses against pathogens. Recently, we demonstrated that MrpH.FimH fusion protein consisting of MrpH from Proteus mirabilis and FimH from Uropathogenic Escherichia coli (UPEC) results in the higher immunogenicity and protection, as compared with FimH and MrpH alone. In this study, we evaluated the innate immunity and adjuvant properties induced by fusion MrpH.FimH through in vitro and in vivo methods. FimH and MrpH.FimH were able to induce significantly higher IL-8 and IL-6 responses than untreated or MrpH alone in cell lines tested. The neutrophil count was significantly higher in the fusion group than other groups. After 6 h, IL-8 and IL-6 production reached a peak, with a significant decline at 24 h post-instillation in both bladder and kidney tissues. Mice instilled with the fusion and challenged with UPEC or P. mirabilis showed a significant decrease in the number of bacteria in bladder and kidney compared to control mice. The results of these studies demonstrate that the use of recombinant fusion protein encoding TLR-4 ligand represents an effective vaccination strategy that does not require the use of a commercial adjuvant. Furthermore, MrpH.FimH was presented as a promising vaccine candidate against UTIs caused by UPEC and P. mirabilis.

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“…Habibi et al [176] used FimH from UPEC and MrpH from MR/P fimbriae from P. mirabilis to evaluate as potential vaccine candidates against uropathogenic infection (UPI). BALB/c animals were immunized with 25 µg/animal of proteins and their combinations via the s.c. route twice with 2-week intervals and challenged transurethrally with 1 × 10 8 CFU of P. mirabilis or UPEC two (UPEC) or seven (P. mirabilis) days post-inoculation.…”

Section: Vaccinesmentioning

confidence: 99%

Secretory System Components as Potential Prophylactic Targets for Bacterial Pathogens

Świętnicki

2021

Biomolecules

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Bacterial secretory systems are essential for virulence in human pathogens. The systems have become a target of alternative antibacterial strategies based on small molecules and antibodies. Strategies to use components of the systems to design prophylactics have been less publicized despite vaccines being the preferred solution to dealing with bacterial infections. In the current review, strategies to design vaccines against selected pathogens are presented and connected to the biology of the system. The examples are given for Y. pestis, S. enterica, B. anthracis, S. flexneri, and other human pathogens, and discussed in terms of effectiveness and long-term protection.

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Evaluation of the effect of MPL and delivery route on immunogenicity and protectivity of different formulations of FimH and MrpH from uropathogenic Escherichia coli and Proteus mirabilis in a UTI mouse model

Cited by 16 publications

References 54 publications

Optimization of an Experimental Vaccine to PreventEscherichia coliUrinary Tract Infection

Optimization of an Experimental Vaccine to PreventEscherichia coliUrinary Tract Infection

Transurethral instillation with fusion protein MrpH.FimH induces protective innate immune responses against uropathogenic Escherichia coli and Proteus mirabilis

Secretory System Components as Potential Prophylactic Targets for Bacterial Pathogens

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