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Published on: October 30, 2013
MV140 Mucosal Vaccine Induces Targeted Immune Response for Enhanced Clearance of Uropathogenic E. coli in
Paula Saz-Leal1,2, Marianne Morris Ligon2, Carmen María Diez-Rivero1
1Inmunotek S.L., 28805 Madrid, Spain.
Abstract:
MV140 is an inactivated whole-cell bacterial mucosal vaccine with proven clinical efficacy against recurrent urinary tract infections (UTIs). These infections are primarily caused by uropathogenic E. coli (UPEC) strains, which are unique in their virulence factors and remarkably diverse. MV140 contains a non-UPEC strain, suggesting that it may induce an immune response against different UPEC-induced UTIs in patients. To verify this, we experimentally evaluated the cellular and humoral responses to UTI89, a prototypical UPEC strain, in mice vaccinated with MV140, as well as the degree of protection achieved in a UPEC UTI89 model of acute cystitis. The results show that both cellular (Th1/Th17) and antibody (IgG/IgA) responses to UTI89 were induced in MV140-immunized mice. MV140 vaccination resulted in an early increased clearance of UTI89 viable bacteria in the bladder and urine following transurethral infection. This was accompanied by a highly significant increase in CD4+ T cells in the bladder and an increase in urinary neutrophils. Collectively, our results support that MV140 induces cross-reactive humoral and cellular immune responses and cross-protection against UPEC strains.
Insights
MV140 vaccination stimulates immune responses against uropathogenic E. coli (UPEC), offering protection against recurrent urinary tract infections (UTIs). This study shows cross-protection against diverse UPEC strains, suggesting broader efficacy.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Recurrent urinary tract infections (UTIs) are often caused by diverse uropathogenic Escherichia coli (UPEC) strains.
- MV140, a bacterial mucosal vaccine, has shown clinical efficacy against UTIs.
- The vaccine contains a non-UPEC strain, raising questions about its cross-protective capabilities.
Purpose of the Study:
- To investigate the cellular and humoral immune responses induced by MV140 against a prototypical UPEC strain (UTI89) in a mouse model.
- To assess the protective efficacy of MV140 against UPEC-induced acute cystitis.
Main Methods:
- Mice were vaccinated with MV140 and subsequently challenged with UPEC UTI89.
- Cellular responses (Th1/Th17, CD4+ T cells) and humoral responses (IgG, IgA) were measured.
- Bacterial clearance in the bladder and urine, and neutrophil levels were assessed.
Main Results:
- MV140 vaccination induced significant Th1/Th17 cellular and IgG/IgA antibody responses to UPEC UTI89.
- Vaccination led to enhanced clearance of UPEC UTI89 from the bladder and urine.
- Increased CD4+ T cells in the bladder and elevated urinary neutrophils were observed post-vaccination.
Conclusions:
- MV140 vaccination elicits cross-reactive humoral and cellular immune responses against UPEC strains.
- The study supports MV140's potential for cross-protection against different UPEC-induced UTIs.
