Oral immunotherapy with short ragweed extract in a novel encapsulated preparation: A double-blind study☆☆☆★★★

Litwin, Allen; Flanagan, Michael; Entis, Gregory; Gottschlich, Gregory; Esch, Robert E.; Gartside, Peter S.; Michael, J.Gabriel

doi:10.1016/s0091-6749(97)70191-x

Cited by 65 publications

(31 citation statements)

References 41 publications

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“…The importance of the allergen concentration for SLIT tablet efficacy has been noted previously [33], and preclinical and human ex vivo biopsy data indicate that the allergen uptake is dose dependent and correlates with the oral mucosal contact time, up to a point of saturation [15,16,19], which may be reached at between 1 and 5 min of mucosal contact time [19]. The allergen release data presented here address both the allergen concentration and the time in solution, and we used the AUC from t = 0 to a given time point as a surrogate parameter for allergen bioavailability.…”

Section: Discussionmentioning

confidence: 89%

“…Since there is no systemic absorption through the oral mucosa during SLIT [12,13,14] and gastrointestinal delivery of allergens to the immune system is unlikely to be efficacious due to breakdown or the dose [15,16], the target organ in SLIT is the local sublingual immune system. This is in line with a mechanism whereby allergen is captured by mucosal antigen-presenting cells that subsequently migrate to the lymph nodes to induce an antiallergic immune response [13,17].…”

Section: Introductionmentioning

confidence: 99%

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Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation

Ohashi-Doi¹,

Kito²,

Du³

et al. 2017

Int Arch Allergy Immunol

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Background: In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined. Methods: The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability. Results: The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet. Conclusions: SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation

Ohashi-Doi¹,

Kito²,

Du³

et al. 2017

Int Arch Allergy Immunol

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“…Treated patients had increased antiragweed IgG and displayed regulated IgE increases during ragweed season [95]. Subsequent double-blind studies demonstrated both the safety and clinical benefit in some patients, as manifested by decreased nasal reactivity and regulated IgE levels during ragweed season [98,99].…”

Section: Oral Allergen Immunotherapymentioning

confidence: 97%

Oral tolerance in the treatment of inflammatory autoimmune diseases

Wardrop

1999

Inflamm. res.

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Oral tolerance refers to the oral administration of protein antigens, which induces a state of systemic nonresponsiveness specific for the fed antigen. This method of inducing immune non-responsiveness has been applied to the prevention and treatment of experimental animal models of autoimmune disease. Extensive research in this area over the past ten years has led to the conclusion that two mechanisms are operative in the mediation of oral tolerance--active suppression and clonal anergy/deletion. A number of factors have been identified that determine which mechanism of tolerance is operative--antigen dose, antigen form, and the timing of antigen administration. Work from these animal models has recently been extended into human clinical trials of multiple sclerosis, rheumatoid arthritis, diabetes, uveitis, and allergy, with differing degrees of success. In this review, a discussion is provided of the animal model systems where oral tolerance has been applied and the clinical trials where an oral tolerization approach has been attempted. Moreover, recent mechanistic studies are reviewed and a model proposed for the induction of oral tolerance.

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“…Studies show clear clinical effectiveness supported by significant symptom improvement and decrease in dosage of drugs required to control the symptoms [35,36]. However, with high doses of allergen, adverse reactions like intestinal bleeding were seen in this form of immunotherapy [37,38].…”

Section: Sublingual Immunotherapy (Slit)mentioning

confidence: 99%

Current immunological approaches for management of allergic rhinitis and bronchial asthma

2009

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A large population world over is affected with allergic diseases and asthma. Pharmacotherapy for allergic diseases and asthma is effective in controlling symptoms but on discontinuation of medication, symptoms reoccur. In contrast, immunotherapy modifies and corrects the underlying pathological immune responses in an antigen-specific manner. Immunotherapy shows an increase in IgG (blocking antibody) that competes with IgE for allergen, inhibiting the release of inflammatory mediators. Recent studies suggest that immunotherapy acts by modifying CD4+ T-cell responses either by immune deviation, T-cell anergy and/or both. Current immunological approaches for management of allergies and asthma involve immunization with native allergen, modified allergen, peptides/cDNA of allergen, anti-IgE, adjuvants coupled allergen, including immunostimulatory DNA sequences, cytokines, and bacterial products. These approaches modulate the immune response and are intended to give long-term benefit.

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Oral immunotherapy with short ragweed extract in a novel encapsulated preparation: A double-blind study☆☆☆★★★

Cited by 65 publications

References 41 publications

Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation

Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation

Oral tolerance in the treatment of inflammatory autoimmune diseases

Current immunological approaches for management of allergic rhinitis and bronchial asthma

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