Safety and immunogenicity of immunotherapy with Bet v 1–derived contiguous overlapping peptides

Spertini, François; Perrin, Yannick; Audran, R; Pellaton, Céline; Boudousquié, Caroline; Barbier, Nathalie; Thierry, Anne‐Christine; Charlon, Vincent; Reymond, Christophe

doi:10.1016/j.jaci.2014.04.001

Cited by 64 publications

(57 citation statements)

References 10 publications

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“…T ere are currently many allergoid preparations containing structurally modif ed allergens in the market with decreased IgE-binding activity. T e prototype of this approach-peptide immunotherapy that uses linear T cell epitope peptides-is showing fruitful results in the treatment of cat and birch pollen allergies with few doses (37,38).…”

Section: Targeting T Cells While Bypassing Ige In Aitmentioning

confidence: 99%

Advances in allergen immunotherapy: Aiming for complete tolerance to allergens

2015

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Allergen-specific immunotherapy (AIT) has been used for more than 100 years as a tolerance-inducing therapy for allergic diseases and represents a potentially curative method of treatment. AIT functions through multiple mechanisms, including regulating T and B cell responses, changing antibody isotypes, and decreasing mediator release and migration of eosinophils, basophils, and mast cells to affected tissues. Despite the relative success of AIT, attempts are being made to improve this therapy in order to overcome problems in standardization, efficacy, safety, long duration of treatment, and costs. These have led to the development of biotechnological products with successful clinical results.

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Section: Targeting T Cells While Bypassing Ige In Aitmentioning

confidence: 99%

Advances in allergen immunotherapy: Aiming for complete tolerance to allergens

2015

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“…Phase IIa/IIb trials using COPs from the Bet v 1 ( Betula verrucosa , birch allergen) sequence showed an up to 40‐fold increase in IgG 4 levels, measured 85 days after the first injection, and a 20‐fold increase in IgG 4 after 60 days of treatment 32. There were no significant differences in specific IgG 4 levels between the low‐ and high‐dose birch COP‐treated patients 4…”

Section: Discussionmentioning

confidence: 99%

A randomized, double‐blind, placebo‐controlled, dose‐finding trial with Lolium perenne peptide immunotherapy

Mösges

Kasche

Raskopf

et al. 2017

Allergy

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BackgroundA novel subcutaneous allergen immunotherapy formulation (gpASIT+™) containing Lolium perenne peptides (LPP) and having a short up‐dosing phase has been developed to treat grass pollen–induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity and safety.MethodsThis prospective, double‐blind, placebo‐controlled, phase IIb, parallel, four‐arm, dose‐finding study randomized 198 grass pollen–allergic adults to receive placebo or cumulative doses of 70, 170 or 370 μg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3 and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks and after completion. Grass pollen–specific immunoglobulins were analysed before and after treatment.ResultsConjunctival provocation test (CPT) response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 μg; P = .023), 46.3% (370 μg), and 38.6% (70 μg) of patients receiving LPP vs 25.6% of patients receiving placebo (modified per‐protocol set). Also, 39% of patients in the 170‐μg group became nonreactive to CPT vs 18% in the placebo group. Facilitated allergen‐binding assays revealed a highly significant (P < .001) dose‐dependent reduction in IgE allergen binding across all treatment groups (70 μg: 17.1%; 170 μg: 18.8%; 370 μg: 26.4%). Specific IgG4 levels increased to 1.6‐fold (70 μg), 3.1‐fold (170 μg) and 3.9‐fold (370 μg) (mPP).ConclusionThree‐week immunotherapy with 170 μg LPP reduced CPT reactivity significantly and increased protective specific antibodies.

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“…Since B-cell epitopes are dependent on the tertiary structure of allergen proteins, changing the tertiary structure through allergen modification, such as in peptide allergens, diminishes the binding strength of IgE to the allergen and may weaken the allergic reaction [11]. T-cell epitopes, however, were not impaired in peptide allergens [12,13]. Reduction of the side effects from AIT using peptides may permit the use of high concentrations of antigens and shorten the treatment period.…”

Section: Peptide Immunotherapymentioning

confidence: 99%

Possibility for Allergy Immunotherapy with Long Synthetic Peptide of Bet V1

Uehara¹,

Hirai²

2016

Otolaryngol (Sunnyvale)

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In allergy immunotherapy (AIT) using peptides, although the choice of T-cell epitope in consideration of the HLA type is important, application to all HLA types is difficult. We recently devised a new method to address this problem in AIT for white birch pollinosis, using long-chain synthetic peptides by dividing the sequence of Bet v1a, the major allergen in white birch pollen, into three peptides that overlap by 10 amino acid residues. Theoretically, these peptides contain all possible T-cell epitopes for any HLA type. Further, these peptides show weak allergenicity and are considered less prone to cause anaphylaxis because the three-dimensional structures differ significantly from the native Bet v1a. The combination of these three peptides of Bet v1a appears to provide an effective, safe form of AIT for white birch pollinosis. This method may thus be applicable to other allergens.

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Safety and immunogenicity of immunotherapy with Bet v 1–derived contiguous overlapping peptides

Cited by 64 publications

References 10 publications

Advances in allergen immunotherapy: Aiming for complete tolerance to allergens

Advances in allergen immunotherapy: Aiming for complete tolerance to allergens

A randomized, double‐blind, placebo‐controlled, dose‐finding trial with Lolium perenne peptide immunotherapy

Possibility for Allergy Immunotherapy with Long Synthetic Peptide of Bet V1

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