Tolerance induction after specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A in children

Rosewich, Martin; Schulze, Johannes; Eickmeier, Olaf; Telles, T.; Rose, Markus A.; Schubert, Ralf; Zielen, Stefan

doi:10.1111/j.1365-2249.2010.04106.x

Cited by 56 publications

(52 citation statements)

References 64 publications

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“…The broadened antibody response caused by the LPS forms therefore increased potential effector functions mediated by the induced HBsAg-specific antibodies. The effects on the antibody response were comparable to those obtained with SmMPLA, with no effects on the IgG1 titers (45)(46)(47). The development of IgG2b was observed regardless of the nature of the LPS form used.…”

Section: Discussionsupporting

confidence: 60%

Adjuvant Activity of Naturally Occurring Monophosphoryl Lipopolysaccharide Preparations from Mucosa-Associated Bacteria

Chilton

Hadel

et al. 2013

Infect Immun

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c Natural heterogeneity in the structure of the lipid A portion of lipopolysaccharide (LPS) produces differential effects on the innate immune response. Gram-negative bacterial species produce LPS structures that differ from the classic endotoxic LPS structures. These differences include hypoacylation and hypophosphorylation of the diglucosamine backbone, both differences known to decrease LPS toxicity. The effect of decreased toxicity on the adjuvant properties of many of these LPS structures has not been fully explored. Here we demonstrate that two naturally produced forms of monophosphorylated LPS, from the mucosa-associated bacteria Bacteroides thetaiotaomicron and Prevotella intermedia, function as immunological adjuvants for antigen-specific immune responses. Each form of mucosal LPS increased vaccination-initiated antigen-specific antibody titers in both quantity and quality when given simultaneously with vaccine antigen preparations. Interestingly, adjuvant effects on initial T cell clonal expansion were selective for CD4 T cells. No significant increase in CD8 T cell expansion was detected. MyD88/Tolllike receptor 4 (TLR4) and TRIF/TLR4 signaling pathways showed equally decreased signaling with the LPS forms studied here as with endotoxic LPS or detoxified monophosphorylated lipid A (MPLA). Natural monophosphorylated LPS from mucosa-associated bacteria functions as a weak but effective adjuvant for specific immune responses, with preferential effects on antibody and CD4 T cell responses over CD8 T cell responses.

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Section: Discussionsupporting

confidence: 60%

Adjuvant Activity of Naturally Occurring Monophosphoryl Lipopolysaccharide Preparations from Mucosa-Associated Bacteria

Chilton

Hadel

et al. 2013

Infect Immun

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“…These Abs are suggested to play a protective role (12,(55)(56)(57)(58) and to mediate the beneficial effects of immunotherapy in allergy as they compete with IgE for the binding of allergens, even if some disagreements still surround this interpretation of the biological role of IgG4 in allergy (59). Interestingly, the isotype switch toward the g4 chain is induced by IL-10, the production of which is up-regulated by SLIT.…”

Section: Discussionmentioning

confidence: 99%

Immunological Effects of Sublingual Immunotherapy: Clinical Efficacy Is Associated with Modulation of Programmed Cell Death Ligand 1, IL-10, and IgG4

Piconi

Trabattoni

Rainone

et al. 2010

The Journal of Immunology

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Sublingual immunotherapy (SLIT) is an alternate route of administration of allergen-specific immunotherapy with an improved safety profile; to clarify the immune mechanisms elicited by this therapy, we analyzed the clinical and immunologic effects of SLIT in patients with a clinical history of ragweed sensitization. To analyze possible difference among immunotherapeutic protocols, we also compared patients receiving preseasonal, seasonal, or prolonged sublingual therapy (≥3 y); patients receiving symptomatic therapy alone were enrolled as well in the study. Clinical and immunological parameters were measured twice in and out of the pollination period. Clinical benefits, as measured by the visual analog scale for symptoms and for use of drugs, were evident in all three groups of individuals receiving immunotherapy, but were significantly better in patients undergoing prolonged SLIT. Immunologically, SLIT resulted in increased IL-10 production, programmed cell death ligand 1 expression, and concentration of allergen-specific IgG4, as well as in the reduction of CD80 and CD86 expression and IL-4 production. SLIT, thus, is associated with modulation of programmed cell death ligand 1 expression and IL-10 synthesis and favors the production of allergen-specific IgG4. These effects are evident from the first pollen season, independently from therapeutic regimen (preseasonal or seasonal) even if a prolonged treatment is necessary to obtain full clinical efficacy. A more detailed understanding of the interaction of allergen and APCs within the oral mucosa will allow improved targeting of allergy vaccine.

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“…Patients treated with placebo had increases in IL-4 and IL-5 production during the pollen season that were inhibited by AIT. Despite these findings, it may take two seasons of treatment for true tolerance to develop based upon allergen-specific IgG and IgG4 levels and associated increase in T-regulatory lymphocytes [30].…”

Section: Tlr4-based Adjuvantsmentioning

confidence: 97%

Novel Approaches of Immunotherapy

Stokes

Casale

2013

Curr Treat Options Allergy

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Opinion statementAllergic diseases affect millions of adults and children in the United States. Allergen immunotherapy has been a treatment option for diseases such as allergic rhinitis, allergic asthma, and venom allergy for the last 100 years. In the last 25 years, alternative approaches to traditional subcutaneous immunotherapy have been developed. The purpose of these new therapies is two-fold: to improve safety and to improve the efficacy of allergen immunotherapy. Aluminum hydroxide has been used as an adjuvant to standard immunotherapy, but due to concerns about side effects, its use has been decreasing. The modification of allergens into allergoids has been an effective therapy in Europe, but at this time no preparations are available for use in the United States. Toll-like receptors have demonstrated mixed results with early trials in the United States, showing promise with the use of a TLR4 agonist, while a TLR9 agonist had disappointing results. Early studies with the use of virus-like particles with and without allergens have shown additional promise, and further trials are currently underway. These novel approaches may improve the immunologic response and often the clinical outcomes for the management of allergic diseases.

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Tolerance induction after specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A in children

Cited by 56 publications

References 64 publications

Adjuvant Activity of Naturally Occurring Monophosphoryl Lipopolysaccharide Preparations from Mucosa-Associated Bacteria

Adjuvant Activity of Naturally Occurring Monophosphoryl Lipopolysaccharide Preparations from Mucosa-Associated Bacteria

Immunological Effects of Sublingual Immunotherapy: Clinical Efficacy Is Associated with Modulation of Programmed Cell Death Ligand 1, IL-10, and IgG4

Novel Approaches of Immunotherapy

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