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Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
Mucosal vaccination of mice with recombinant Proteus mirabilis structural fimbrial proteins
Paola Scavone1, Vanessa Sosa, Rafael Pellegrino
1Laboratorio de Microbiología, Instituto de Investigaciones Biológicas Clemente Estable, Avda. Italia 3318, Montevideo CP11600, Uruguay.
Abstract:
Proteus mirabilis, a common cause of urinary tract infection (UTI), expresses several types of fimbria including mannose-resistant/Proteus-like fimbriae (MRP), uroepithelial cell adhesin (UCA), renamed non-agglutinating fimbriae (NAF) by some authors, and P. mirabilis fimbriae (PMF), which are potentially involved in adhesion to the uroepithelium. In this study, we immunised different groups of mice with recombinant structural subunits of these fimbriae (MrpA, UcaA and PmfA) using two mucosal routes (nasal and transurethral) and we transurethrally challenged the animals with a P. mirabilis uropathogenic isolate. Induction of specific serum and urine IgG and IgA was measured to assess the potential role of the humoral immune response in protection against experimental ascending P. mirabilis UTI. Intranasally MrpA- and UcaA-immunised mice were protected against P. mirabilis ascending UTI, since recovery of bacteria from kidneys and bladders was significantly lower than in PBS-treated mice, and both fimbrial subunits significantly induced specific serum and urine antibodies. Only MrpA and PmfA transurethrally immunised animals were protected only at the kidney level, and in this case only MrpA-immunised mice exhibited significant serum IgG induction. Correlation analysis did not show a significant relationship between serum and urine specific antibody response and protection observed against infection. Our results suggest that an immunisation strategy based on structural fimbrial proteins may be useful to prevent P. mirabilis UTI. Further studies are being carried out to characterise the immune and inflammatory response induced by P. mirabilis recombinant fimbrial subunits.
Insights
Vaccinating mice with specific Proteus mirabilis fimbrial proteins via nasal or transurethral routes offered protection against urinary tract infections (UTIs). Nasal immunization with MrpA and UcaA showed significant protection in kidneys and bladders.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Proteus mirabilis is a common cause of urinary tract infections (UTIs).
- Fimbriae, such as mannose-resistant/Proteus-like (MRP), uroepithelial cell adhesin (UCA), and P. mirabilis fimbriae (PMF), are key virulence factors involved in bacterial adhesion to the urinary tract lining.
- Developing effective preventative strategies against P. mirabilis UTIs is crucial.
Purpose of the Study:
- To evaluate the protective efficacy of immunizing mice with recombinant structural subunits of P. mirabilis fimbriae (MrpA, UcaA, PmfA).
- To assess the role of mucosal (nasal and transurethral) immunization routes in inducing protective immunity against experimental P. mirabilis UTI.
- To investigate the correlation between humoral immune responses (serum and urine antibodies) and protection.
Main Methods:
- Mice were immunized intranasally or transurethrally with recombinant MrpA, UcaA, or PmfA subunits.
- Animals were subsequently challenged with a uropathogenic P. mirabilis isolate via the transurethral route.
- Specific serum and urine IgG and IgA levels were measured.
- Bacterial load in kidneys and bladders was quantified to assess protection.
Main Results:
- Intranasal immunization with MrpA and UcaA significantly reduced bacterial recovery from kidneys and bladders, indicating protection against ascending UTI.
- Transurethral immunization with MrpA and PmfA provided protection only at the kidney level.
- Both intranasal MrpA and UcaA immunizations induced significant specific serum and urine antibodies.
- No significant correlation was found between specific antibody levels and the observed protection.
Conclusions:
- Mucosal immunization strategies using structural fimbrial proteins, particularly MrpA and UcaA via the nasal route, show promise for preventing P. mirabilis UTIs.
- While antibody induction is observed, the direct correlation with protection is not straightforward, suggesting other immune mechanisms may be involved.
- Further research is needed to fully characterize the immune and inflammatory responses elicited by these fimbrial subunits.

