RESUMO
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.
RESUMO
BACKGROUND: A prospective, descriptive, and multicenter research that included 1104 women with three or more uncomplicated UTIs following immunoprophylaxis with Uromune® vaccine between 2011 and 2022 is presented. OBJECTIVE: to analyze the efficacy of Uromune® and perform a follow-up protocol. VARIABLES: age; bacteria; number of UTIs at baseline and at 3, 6, and 12 months of follow-up; distribution according to age and months of the year; therapy with polybacterial vaccine or autovaccine. Efficacy was defined as 0-2 UTIs during follow-up. Patients were divided into Group 1, with 3-4 UTIs at baseline, and Group 2, with 5 or more. RESULTS: Average age was 72. Escherichia coli represented 64.3% of infections. Overall efficacy was 91.7%, 82.3%, and 57.6% at 3, 6, and 12 months. Efficacy in patients treated with vaccines was 95.8%, 88.4%, and 56.1%, and with autovaccines it was 85.7%, 73.6%, and 60.2%. Results were statistically significant in relation to vaccines (p < 0.05). Group 1 represented 65.2% and Group 2 represented 34.8%. Group 1 had an efficacy of 97.7%, 91.1%, and 64.7% and Group 2 had an efficacy of 80.2%, 64.3%, and 40%. Results were statistically significant in Group 1 (p < 0.05). CONCLUSIONS: Patients at baseline with less than five UTIs will have better result and would benefit from a prophylaxis protocol with Uromune®.
RESUMO
OBJECTIVES: To determine, firstly, whether MV140 reduces rates of recurrent urinary tract infections (rUTIs) in patients older than 65 years, measured as the number of urinary tract infections (UTIs) detected over 12 months following the completion of a 3-month treatment course and, additionally, to assess the number of re-admissions to the emergency department, the rate of antibiotic use for UTIs, the safety profile of MV140, and quality of life. MATERIALS AND METHODS: This is a multicentre, double-blind, randomized controlled trial with two arms. Patients will be randomized and allocated to receive either a 3-month course of MV140 or placebo (two sublingual sprays daily). Participants will have 3-monthly consultations with the investigator for 12 months to assess differences in rates of rUTIs between the two groups. Study candidates will be identified and recruited from inpatient and outpatient clinics across Sydney via referral to the investigation team. After obtaining consent, participants will undergo initial study consultations including urine microscopy and culture, uroflowmetry, and bladder scan to assess postvoid residual urine volume. Participants will be randomized and provided with a unique trial number. Electronic medical records will be reviewed to collect relevant information. Participants will be provided with a study diary to record relevant data. RESULTS: Follow-up consultations will be conducted every 3 months for a 12-month duration, during which the study diary will be reviewed. These follow-up consultations will primarily occur via telephone review, however, there will be flexibility for in-person reviews for participants who find telephone consultation prohibitively difficult. CONCLUSION: This is a multicentre, double-blinded, randomised control trial, the first in Australia to assess the safety and efficacy of MV140 Uromune vaccine in prevention of recurrent UTIs. Results have been promissing in the global literatures.
Assuntos
Microscopia , Infecções Urinárias , Humanos , Qualidade de Vida , Encaminhamento e Consulta , Urinálise , Telefone , Método Duplo-Cego , Infecções Urinárias/prevenção & controle , Infecções Urinárias/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Introduction: Recurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems all over the world. Antibiotics and antifungals are widely used for such infectious diseases, which is linked with microbial resistances and microbiota deleterious effects. The development of novel approaches for genitourinary tract infections (GUTIs) such as trained immunity-based vaccines (TIbV) is therefore highly required. MV140 is a sublingual whole-cell heat-inactivated polybacterial preparation with demonstrated clinical efficacy for RUTIs. The sublingual heat-inactivated Candida albicans vaccine V132 has been developed for RVVCs. We previously showed that the combination of MV140 and V132 promotes potent Th1/Th17 and regulatory T-cell responses against antigens contained in the formulation and unrelated antigens. The specific contribution of each preparation to such effects and the underlying molecular mechanisms remain incompletely understood. Methods: PBMC and monocytes were isolated from healthy donors and in vitro stimulated with V132, MV140 or MV140/V132. After 6 days of resting, cells were reestimulated with LPS and MV140. Analysis of cytokine production by ELISA, Seahorse assays for functional metabolic experiments and chromatin immunoprecipitation assays were performed. BALB/c mice were intraperitoneally and sublingually immunized with V132. Results: We uncover that V132 induces trained immunity in human PBMCs and purified monocytes, significantly increasing the responses triggered by subsequent stimulation with MV140. Mechanistically, V132 drives metabolic rewiring towards increased glycolysis and oxidative phosphorylation and induces epigenetic reprogramming that enhances the transcription of the pro-inflammatory genes IL6 and TNFA. Splenocytes and peritoneal cells from V132-immunize mice show increased responses upon in vitro stimulation with MV140. Remarkably, splenocytes from sublingually V132-immunized and MV140 in vivo treatment mice show stronger Th17 responses than mice exposed to excipients upon in vitro stimulation with MV140. Conclusion: Overall, we provide novel mechanistic insights into how V132-induced trained immunity enhances both innate and adaptive immune responses triggered by MV140, which might open the door for new interventions for GUTIs with important clinical implications.
Assuntos
Candidíase Mucocutânea Crônica , Infecções Urinárias , Vacinas , Humanos , Camundongos , Animais , Candida albicans , Leucócitos Mononucleares , Imunidade TreinadaRESUMO
BACKGROUND: The objective of this article was to assess the long-term efficacy and safety of the MV140 vaccine to prevent recurrent urinary tract infections (UTIs). METHODS: This is a prospective, descriptive, comparative and multicenter study of 1003 patients with 3 or more urinary infections for 12 months, treated with the MV140 vaccine from 2011 to 2021. VARIABLES: Age, gender, urinary infections at 3, 6 and 12 months, distribution according to age and months of the year, smoking, use of MV140 vaccines and autovaccines. RESULTS: Mean age was 78 and 82.7% were women. At baseline, 84.1% had 3 to 5 infections. According to age, 68.6% had >70 years. There were more consultations in March (12.3%) and fewer in August (4.4%). Smokers represented 24.6% and 21.8% follow autovaccines. Results at 3 months: 0 UTI 45%, 1 UTI 31.3%, 2 UTI 19.2%. 6 months: 0 UTI 29.3%, 1 UTI 33.2%, 2 UTI 24.3%. 12 months: 0 UTI 9%, 1 UTI 28.2%, 2 UTI 17.5%. Smokers: 0-1 UTI 80.2% (3 months), 65.5% (6 months), 53.9% (12 months). Non-smokers: 0-1 UTI 85.8% (3 months), 66.8% (6 months), 20% (12 months). p = 0.41, 0.27 and 0.21 respectively. Vaccines: 0-1 UTI 74.5% (3 months), 61% (6 months), 38.8% (12 months). Autovaccines: 0-1 UTI 82.7% (3 months), 68 % (6 months), 28.2% (12 months). p = 0.04, 0.25 and 0.63 respectively. CONCLUSIONS: MV140 reduced the number of UTI to 0-2 in 95.5% at 3 months, 86.8% at 6 months and 54.7% at 12 months. Smoking did not worsen the response of MV140. Autovaccines achieved better results than vaccines only at 3 months. Adverse effects represented 1.49%, but no patient had to abandon treatment.
Assuntos
Autovacinas , Infecções Urinárias , Vacinas , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Seguimentos , Estudos Prospectivos , Autovacinas/uso terapêutico , Recidiva , Infecções Urinárias/prevenção & controle , Infecções Urinárias/tratamento farmacológico , Vacinas/uso terapêuticoRESUMO
PURPOSE: This study aimed to determine the effectiveness of whole-cell bacterial immunotherapy, i.e. MV140 and autovaccines, in reducing the number ofurinary tract infections (UTIs)in frail elderly patients with recurrent UTI (RUTI). METHOD: A prospective cohort observational study was performed including 200 frail elderly subjects suffering RUTI, both females and males, between 2016 and 2018. The effectiveness of autovaccines and the polybacterial formulation MV140 (Uromune®), consisting ofwhole-cell heat-inactivated Escherichia coli25%, Klebsiella pneumoniae25%, Proteus vulgaris25% andEnterococcus faecalis25% were evaluated. Subjects initiated a 3-month sublingually daily course with MV140 or autovaccine, either first treatment or a new course if they had been previously vaccinated prior to inclusion in the study. Number of UTIs and quality of life (QoL, SF-36 score) were measured in the different study groups. RESULTS: The mean age for participants was 82.67 (SD, 7.12) for female and 80.23 (SD, 11.12) for male subjects. In all groups, 12â¯months following bacterial immunotherapy, the number of UTIs significantly decreased compared to before the treatment with autovaccine or MV140: the rate of reduction ranged between 7- and 40-fold. An increase in QoL scoring was also observed in any study group. When comparing medical interventions, MV140 conferred significantly higher benefit than autovaccines. For previously vaccinated individuals, a new 3-month course with MV140 or autovaccines provided further clinical improvement. CONCLUSIONS: MV140 and autovaccines emerge as valuable immunoprophylaxis for the management of RUTI in the frail elderly, contributing to an improvement in patient's quality of life. Herein, MV140 has shown to confer a higher effectiveness compared to autovaccines, regardless sex or course of treatment.
Assuntos
Qualidade de Vida , Infecções Urinárias , Idoso , Feminino , Idoso Fragilizado , Humanos , Imunização , Masculino , Estudos Prospectivos , Infecções Urinárias/prevenção & controleRESUMO
Introduction: Conventional or biologic disease-modifying anti-rheumatic drugs (DMARDs) are the mainstay of treatment for systemic autoimmune disease (SAD). Infectious complications are a major concern in their use. Objective: To evaluate the clinical benefit of sublingual mucosal polybacterial vaccines (MV130 and MV140), used to prevent recurrent respiratory and urinary tract infections, in patients with SAD and secondary recurrent infections following conventional or biologic DMARDs. Methods: An observational study in SAD patients with recurrent respiratory tract infections (RRTI) and/or recurrent urinary tract infections (RUTI) was carried out. All patients underwent mucosal (sublingual) vaccination with MV130 for RRTI or with MV140 for RUTI daily for 3 months. Clinical evaluation was assessed during 12 months of follow-up after the first dose, i.e., 3 months under treatment and 9 months once discontinued, and compared with the previous year. Results: Forty-one out of 55 patients completed 1-year follow-up. All patients were on either conventional or biologic DMARDs. A significant decrease in the frequency of RUTI (p<0.001), lower respiratory tract infections (LRTI) (p=0.009) and upper respiratory tract infections (URTI) (p=0.006) at 12-mo with respect to the previous year was observed. Antibiotic prescriptions and unscheduled medical visits decreased significantly (p<0.020) in all groups. Hospitalization rate also declined in patients with RRTI (p=0.019). The clinical benefit demonstrated was concomitant to a significant increase in both anti-S. pneumoniae IgA and IgG antibodies following MV130 vaccination. Conclusions: Sublingual polybacterial vaccines prevent recurrent infections in patients with SAD under treatment with immunosuppressant therapies, supporting a broad non-specific anti-infectious effect in these patients.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Vacinas Bacterianas/imunologia , Imunossupressores/uso terapêutico , Reinfecção/prevenção & controle , Infecções Respiratórias/prevenção & controle , Infecções Urinárias/prevenção & controle , Vacinação , Adulto , Idoso , Doenças Autoimunes/imunologia , Vacinas Bacterianas/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Recurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems with high socio-economic impact worldwide. Antibiotic and antifungal prophylaxis remain the gold standard treatments for RUTIs and RVVCs, contributing to the massive rise of antimicrobial resistance, microbiota alterations and co-infections. Therefore, the development of novel vaccine strategies for these infections are sorely needed. The sublingual heat-inactivated polyvalent bacterial vaccine MV140 shows clinical efficacy for the prevention of RUTIs and promotes Th1/Th17 and IL-10 immune responses. V132 is a sublingual preparation of heat-inactivated Candida albicans developed against RVVCs. A vaccine formulation combining both MV140 and V132 might well represent a suitable approach for concomitant genitourinary tract infections (GUTIs), but detailed mechanistic preclinical studies are still needed. Herein, we showed that the combination of MV140 and V132 imprints human dendritic cells (DCs) with the capacity to polarize potent IFN-γ- and IL-17A-producing T cells and FOXP3+ regulatory T (Treg) cells. MV140/V132 activates mitogen-activated protein kinases (MAPK)-, nuclear factor-κB (NF-κB)- and mammalian target of rapamycin (mTOR)-mediated signaling pathways in human DCs. MV140/V132 also promotes metabolic and epigenetic reprogramming in human DCs, which are key molecular mechanisms involved in the induction of innate trained immunity. Splenocytes from mice sublingually immunized with MV140/V132 display enhanced proliferative responses of CD4+ T cells not only upon in vitro stimulation with the related antigens contained in the vaccine formulation but also upon stimulation with phytohaemagglutinin. Additionally, in vivo sublingual immunization with MV140/V132 induces the generation of IgG and IgA antibodies against all the components contained in the vaccine formulation. We uncover immunological mechanisms underlying the potential mode of action of a combination of MV140 and V132 as a novel promising trained immunity-based vaccine (TIbV) for GUTIs.
Assuntos
Antígenos de Bactérias/administração & dosagem , Antígenos de Fungos/administração & dosagem , Infecções Bacterianas/prevenção & controle , Vacinas Bacterianas/administração & dosagem , Candidíase Vulvovaginal/terapia , Vacinas Fúngicas/administração & dosagem , Infecções Urinárias/prevenção & controle , Vacinas Combinadas/administração & dosagem , Animais , Antígenos de Bactérias/imunologia , Antígenos de Fungos/imunologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/metabolismo , Infecções Bacterianas/microbiologia , Vacinas Bacterianas/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Candidíase Vulvovaginal/imunologia , Candidíase Vulvovaginal/metabolismo , Candidíase Vulvovaginal/microbiologia , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Feminino , Vacinas Fúngicas/imunologia , Humanos , Ativação Linfocitária/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Fenótipo , Infecções Urinárias/imunologia , Infecções Urinárias/metabolismo , Infecções Urinárias/microbiologia , Vacinação , Vacinas Combinadas/imunologiaRESUMO
OBJECTIVE: To compare the clinical impact of a prophylactic treatment with sublingual immunostimulation in the prevention of recurrent urinary tract infections (rUTIs) with the use of antibiotics. MATERIAL AND METHODS: Retrospective cohort study evaluating the medical records of 669 women with rUTIs; 339 had a 6-month prophylaxis with antibiotics and 360 a 3-month prophylaxis with a sublingual bacterial preparation (MV 140-Uromune®). The time frame after the prophylaxis-period until the appearance of a new infection (assessed by uroculture) was scored and followed during 1 year. The absolute risk reduction (ARR) and number needed to treat (NNT) were also calculated. RESULTS: All patients treated with antibiotics experienced a new UTI during the scoring period of 12 months, being 19 days the median number of days free of UTIs (range 5-300). In the group treated with the bacterial preparation, 35 (9.7%) patients experienced an UTI in the same period. Kaplan-Meier curves comparing the accumulated survival (disease-free time) between both groups were significant different (P < 0.0001). The absolute risk reduction (ARR) was 90.28% (87.18-93.38) and the number needed to treat (NNT) 1.1 (1.1-1.1). CONCLUSIONS: These results suggest that the treatment with this bacterial preparation significantly reduces the incidence of rUTIs, arising as an effective strategy to reduce the frequency of rUTIs. It reduces antibiotic consumption, matching the current recommendations due to the raise of antimicrobial resistance. Randomized, double-blind and placebo-controlled, clinical trials are needed to establish, more accurately, the clinical impact of this bacterial preparation in patients with rUTIs.