MV140, a sublingual polyvalent bacterial preparation to treat recurrent urinary tract infections, licenses human dendritic cells for generating Th1, Th17, and IL-10 responses via Syk and MyD88

Benito-Villalvilla, Cristina; Cirauqui, Cristina; Díez-Rivero, Carmen M.; Casanovas, Miguel; Subiza, J L; Palomares, Óscar

doi:10.1038/mi.2016.112

Cited by 58 publications

(70 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The sublingual epithelium contains a dense network of dendritic cells that play an essential role in linking innate and adaptive immune responses [13]. Recent studies of the immunological mechanisms underlying the clinical benefits of Uromune ® in the treatment of R-UTI have shown that sublingual vaccines stimulate human dendritic cells, with the ability to generate Th1, Th17, and IL-10-producing T cells [14].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Efficacy of a Sublingual Bacterial Vaccine in the Prophylaxis of Recurrent Urinary Tract Infection

et al. 2020

View full text Add to dashboard Cite

Objectives: Recurrent urinary tract infections (R-UTIs) are very common amongst women, and alternatives to antibacterial prophylaxis are necessary. This study evaluates the effectiveness of a sublingual bacterial vaccine for the prophylaxis of R-UTIs. Methods: We conducted a quasi-experimental pretest-posttest study of 166 women diagnosed with R-UTIs. Both before and after the start of treatment with the vaccine, we analysed the total number of R-UTI episodes, the urine culture results, and the type and number of antibiotic packages consumed. Symptoms and urine cultures were evaluated 3, 6, 9, 12, 18, and 24 months after initiating treatment with the vaccine. Results: The mean time of follow-up after vaccination was 1.7 years. After vaccination, there was a 54.6% reduction in episodes of UTI, and a 56.2% reduction in positive urine cultures. At 3 months, 74.4% of the patients had no R-UTI, the rate falling to 68.1% at 6 months, 52.4% at 12 months, and 44.5% at 24 months. The cumulative probability of maintaining negative urine cultures was 76% at 3 months, 37% at 12 months, and 18% at 2 years. Conclusions: The use of a sublingual bacterial vaccine for the prophylaxis of R-UTIs in women is an effective treatment that contributes to a reduction in the number of UTI episodes.

show abstract

Section: Discussionmentioning

confidence: 99%

Analysis of the Efficacy of a Sublingual Bacterial Vaccine in the Prophylaxis of Recurrent Urinary Tract Infection

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In this sense, besides antigen penetration across the sublingual epithelial barrier, an active capture by intraepithelial DCs25 or through the ductal epithelial cells26 has been described, even for particulate antigens, silica beads, or microbes 26. In fact, bigger structures than PM‐allergoids, like particles of different sizes15, 27 or whole cell bacteria,28, 29 have also been successfully used for immunization through the sublingual route.…”

Section: Discussionmentioning

confidence: 99%

Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice

Soria

López-Relaño

Viñuela

et al. 2018

Allergy

View full text Add to dashboard Cite

BackgroundPolymerized allergoids coupled to nonoxidized mannan (PM‐allergoids) may represent novel vaccines targeting dendritic cells (DCs). PM‐allergoids are better captured by DCs than native allergens and favor Th1/Treg cell responses upon subcutaneous injection. Herein we have studied in mice the in vivo immunogenicity of PM‐allergoids administered sublingually in comparison with native allergens.MethodsThree immunization protocols (4‐8 weeks long) were used in Balb/c mice. Serum antibody levels were tested by ELISA. Cell responses (proliferation, cytokines, and Tregs) were assayed by flow cytometry in spleen and lymph nodes (LNs). Allergen uptake was measured by flow cytometry in myeloid sublingual cells.ResultsA quick antibody response and higher IgG2a/IgE ratio were observed with PM‐allergoids. Moreover, stronger specific proliferative responses were seen in both submandibular LNs and spleen cells assayed in vitro. This was accompanied by a higher IFNγ/IL‐4 ratio with a quick IL‐10 production by submandibular LN cells. An increase in CD4+ CD25high FOXP3+ Treg cells was detected in LNs and spleen of mice treated with PM‐allergoids. These allergoids were better captured than native allergens by antigen‐presenting (CD45+ MHC‐II +) cells obtained from the sublingual mucosa, including DCs (CD11b+) and macrophages (CD64+). Importantly, all the differential effects induced by PM‐allergoids were abolished when using oxidized instead of nonoxidized PM‐allergoids.ConclusionOur results demonstrate for the first time that PM‐allergoids administered through the sublingual route promote the generation of Th1 and FOXP3+ Treg cells in a greater extent than native allergens by mechanisms that might well involve their better uptake by oral antigen‐presenting cells.

show abstract

“…Collectively, we demonstrated that MV130, a sublingual whole inactivated PBP that prevents infections in patients suffering from RRTIs, directly acts on human DCs promoting the generation of TLR-mediated signalling pathways under the control of IL-10. We have recently shown that MV140, a sublingual PBP formulated with a different composition of whole-inactivated bacteria to treat recurrent urinary tract infections, also generates Th1, Th17 and IL-10 immune responses [50]. Interestingly, the mechanisms underlying the effects of MV140 (75% Gram-negative/25% Gram-positive) depend on spleen tyrosine kinase (Syk)-mediated signalling pathways in cooperation with MyD88 [50], which are different to those reported in this study for MV130 (90% Grampositive/10% Gram-negative).…”

Section: Discussionmentioning

confidence: 99%

“…We have recently shown that MV140, a sublingual PBP formulated with a different composition of whole-inactivated bacteria to treat recurrent urinary tract infections, also generates Th1, Th17 and IL-10 immune responses [50]. Interestingly, the mechanisms underlying the effects of MV140 (75% Gram-negative/25% Gram-positive) depend on spleen tyrosine kinase (Syk)-mediated signalling pathways in cooperation with MyD88 [50], which are different to those reported in this study for MV130 (90% Grampositive/10% Gram-negative). Although TLRs contribute to the final outcomes in both cases, the relative contribution in MV130 and MV140 is also different (Supporting Information Fig.…”

Section: Discussionmentioning

confidence: 99%

Human dendritic cells activated with MV130 induce Th1, Th17 and IL‐10 responses via RIPK2 and MyD88 signalling pathways

et al. 2017

View full text Add to dashboard Cite

Recurrent respiratory tract infections (RRTIs) are the first leading cause of community‐ and nosocomial‐acquired infections. Antibiotics remain the mainstay of treatment, enhancing the potential to develop antibiotic resistances. Therefore, the development of new alternative approaches to prevent and treat RRTIs is highly demanded. Daily sublingual administration of the whole heat‐inactivated polybacterial preparation (PBP) MV130 significantly reduced the rate of respiratory infections in RRTIs patients, however, the immunological mechanisms of action remain unknown. Herein, we study the capacity of MV130 to immunomodulate the function of human dendritic cells (DCs) as a potential mechanism that contribute to the clinical benefits. We demonstrate that DCs from RRTIs patients and healthy controls display similar ex vivo immunological responses to MV130. By combining systems biology and functional immunological approaches we show that MV130 promotes the generation of Th1/Th17 responses via receptor‐interacting serine/threonine‐protein kinase‐2 (RIPK2)‐ and myeloid‐differentiation primary‐response gene‐88 (MyD88)‐mediated signalling pathways under the control of IL‐10. In vivo BALB/c mice sublingually immunized with MV130 display potent systemic Th1/Th17 and IL‐10 responses against related and unrelated antigens. We elucidate immunological mechanisms underlying the potential way of action of MV130, which might help to design alternative treatments in other clinical conditions with high risk of recurrent infections.

show abstract

MV140, a sublingual polyvalent bacterial preparation to treat recurrent urinary tract infections, licenses human dendritic cells for generating Th1, Th17, and IL-10 responses via Syk and MyD88

Cited by 58 publications

References 50 publications

Analysis of the Efficacy of a Sublingual Bacterial Vaccine in the Prophylaxis of Recurrent Urinary Tract Infection

Analysis of the Efficacy of a Sublingual Bacterial Vaccine in the Prophylaxis of Recurrent Urinary Tract Infection

Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice

Human dendritic cells activated with MV130 induce Th1, Th17 and IL‐10 responses via RIPK2 and MyD88 signalling pathways

Contact Info

Product

Resources

About