Novel vaccines targeting dendritic cells by coupling allergoids to nonoxidized mannan enhance allergen uptake and induce functional regulatory T cells through programmed death ligand 1

Sirvent, Sofía; Soria, Irene; Cirauqui, Cristina; Cases, Bárbara; Manzano, Ana I.; Díez-Rivero, Carmen M.; Reche, Pedro A.; López-Relaño, Juan; Martı́nez-Naves, Eduardo; Cañada, F. Javier; Jiménez‐Barbero, Jesús; Subiza, Javier; Casanovas, Miguel; Fernández-Caldas, Enrique; Subiza, José Luis; Palomares, Óscar

doi:10.1016/j.jaci.2016.02.029

Cited by 96 publications

(157 citation statements)

References 60 publications

(103 reference statements)

Supporting

Mentioning

150

Contrasting

Unclassified

Order By: Relevance

“…We previously demonstrated that PM‐allergoids are much better captured than native allergens by human16 and canine17 DCs and that this property is lost upon mannan oxidation. Here we show that this is also the case in mice when assessing antigen‐presenting cells (CD45 + MHC‐II + ) from the sublingual mucosa.…”

Section: Discussionmentioning

confidence: 99%

“…N, PM, and PM‐OX allergen preparations were equally labeled with Alexa 488 maleimide (Thermo Fisher Scientific) and allergen uptake performed as described 16. Briefly, cells (3 × 10 5 ) were incubated (30 minutes at 37°C) with 100 μg/mL of each labeled preparation in RPMI.…”

Section: Methodsmentioning

confidence: 99%

“…We previously reported that polymerized allergoids coupled to nonoxidized mannan derived from Saccharomyces cerevisae (PM‐allergoids) are better captured than native allergens by human16 and canine17 DCs. PM‐allergoids are taken up by DCs very rapidly through a receptor‐mediated mechanism involving C‐type lectin receptors 16.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…PM‐allergoids are taken up by DCs very rapidly through a receptor‐mediated mechanism involving C‐type lectin receptors 16. Besides their better uptake, these glycoconjugates are rendered hypoallergenic16, 17, 18 and able to activate DCs to promote the induction of functional FOXP3 + Treg cells,16 thus with improved features for allergen immunotherapy 19. These properties may be especially relevant for SLIT due to the very short time the allergens are available to mucosal DCs, which might well explain the high allergen doses needed for clinical efficacy in SLIT 12, 14.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

show abstract

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

et al. 2017

Self Cite

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

Pru p 3‐Glycodendropeptides Based on Mannoses Promote Changes in the Immunological Properties of Dendritic and T‐Cells from LTP‐Allergic Patients

Palomares

Ramos‐Soriano

Gómez

et al. 2019

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope Glycodendropeptides (GDPs) functionalized with mannose can enhance allergen interaction with dendritic cells (DCs) via C‐type lectin receptors (CLRs), modulating the immune response. They can present multiple peptides and have potential applications for diagnosis and treatment of food allergy (FA). The immune response induced by GDPs with mannose and Pru p 3 peptides (mono/tetravalent) with ester (D1ManPrup3/D4ManPrup3) or ether linkers (D1Man‐O‐Prup3/D4Man‐O‐Prup3) in lipid‐transfer‐protein‐allergic patients and tolerant controls is analyzed. Methods and results The immunological response induced by GDPs is studied by assessing monocyte‐derived‐DC maturation, lymphocyte proliferation, cytokine production, and basophil response by flow cytometry. DnManPrup3 was recognized by DCs via CLRs inducing DC maturation in all subjects. However, CCR7 expression is significantly upregulated in allergic patients compared to tolerant controls. These changes correlate with lymphocyte proliferation and specific production of Th2/Th1 cytokines in allergic patients. Moreover, D1ManPrup3 does not induce basophil activation. Conclusion DnManPrup3 induces changes in DC maturation and lymphocyte proliferation, indicating specific recognition via CLRs. Prup3‐GDPs are recognized by immune cells, inducing a specific immune response and modulating the immunological response in FA patients. The specific geometry of D1ManPrup3 in particular makes it a potential candidate for specific immunotherapy development.

show abstract

Novel vaccines targeting dendritic cells by coupling allergoids to nonoxidized mannan enhance allergen uptake and induce functional regulatory T cells through programmed death ligand 1

Abstract: Allergoids conjugated to nonoxidized mannan represent suitable vaccines for AIT. Our findings might also be of the utmost relevance to development of therapeutic interventions in other immune tolerance-related diseases.

Cited by 96 publications

References 60 publications

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

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

Pru p 3‐Glycodendropeptides Based on Mannoses Promote Changes in the Immunological Properties of Dendritic and T‐Cells from LTP‐Allergic Patients

Contact Info

Product

Resources

About