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Novel birch pollen specific immunotherapy formulation based on contiguous overlapping peptides.

ABSTRACT: BACKGROUND:Synthetic contiguous overlapping peptides (COPs) may represent an alternative to allergen extracts or recombinant allergens for allergen specific immunotherapy. In combination, COPs encompass the entire allergen sequence, providing all potential T cell epitopes, while preventing IgE conformational epitopes of the native allergen. METHODS:Individual COPs were derived from the sequence of Bet v 1, the major allergen of birch pollen, and its known crystal structure, and designed to avoid IgE binding. Three sets of COPs were tested in vitro in competition ELISA and basophil degranulation assays. Their in vivo reactivity was determined by intraperitoneal challenge in rBet v 1 sensitized mice as well as by skin prick tests in volunteers with allergic rhinoconjunctivitis to birch pollen. RESULTS:The combination, named AllerT, of three COPs selected for undetectable IgE binding in competition assays and for the absence of basophil activation in vitro was unable to induce anaphylaxis in sensitized mice in contrast to rBet v 1. In addition no positive reactivity to AllerT was observed in skin prick tests in human volunteers allergic to birch pollen. In contrast, a second set of COPs, AllerT4-T5 displayed some residual IgE binding in competition ELISA and a weak subliminal reactivity to skin prick testing. CONCLUSIONS:The hypoallergenicity of contiguous overlapping peptides was confirmed by low, if any, IgE binding activity in vitro, by the absence of basophil activation and the absence of in vivo induction of allergic reactions in mouse and human. TRIAL REGISTRATION:ClinicalTrials.gov NCT01719133.

SUBMITTER: Pellaton C

PROVIDER: S-EPMC3672070 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Novel birch pollen specific immunotherapy formulation based on contiguous overlapping peptides.

Pellaton Céline C Perrin Yannick Y Boudousquié Caroline C Barbier Nathalie N Wassenberg Jacqueline J Corradin Giampietro G Thierry Anne-Christine AC Audran Régine R Reymond Christophe C Spertini François F

Clinical and translational allergy 20130601 1

<h4>Background</h4>Synthetic contiguous overlapping peptides (COPs) may represent an alternative to allergen extracts or recombinant allergens for allergen specific immunotherapy. In combination, COPs encompass the entire allergen sequence, providing all potential T cell epitopes, while preventing IgE conformational epitopes of the native allergen.<h4>Methods</h4>Individual COPs were derived from the sequence of Bet v 1, the major allergen of birch pollen, and its known crystal structure, and de ...[more]

PMID: 23725004

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Project description:AimTo investigate whether birch pollen allergy symptoms are linked with gut microbiota changes and whether probiotics have an effect on these.MethodsForty seven children with confirmed birch pollen allergy were randomized to receive either a probiotic combination of Lactobacillus acidophilus (L. acidophilus) NCFM (ATCC 700396) and Bifidobacterium lactis (B. lactis) Bl-04 (ATCC SD5219) or placebo in a double-blind manner for 4 mo, starting prior to onset of the birch pollen season. Symptoms were recorded in a diary. Blood samples were taken for analysis of cytokines and eosinophils. Fecal samples were analysed for microbiota components, calprotectin and IgA. Nasal swabs were taken for analysis of eosinophils.ResultsThe pollen season induced a reduction in Bifidobacterium, Clostridium and Bacteroides which could not be prevented by the probiotic intervention. During the intervention, significantly higher numbers of B. lactis 11.2 x 10(7) +/- 4.2 x 10(7) vs 0.1 x 10(7) +/- 0.1 x 10(7) bacteria/g feces (P < 0.0001) and L. acidophilus NCFM 3.5 x 10(6) +/- 1.3 x 10(6) vs 0.2 x 10(6) +/- 0.1 x 10(6) bacteria/g feces (P < 0.0001) were observed in the probiotic group compared to the placebo group. During May, there was a tendency for fewer subjects, (76.2% vs 95.2%, P = 0.078) to report runny nose, while during June, fewer subjects, 11.1% vs 33.3%, reported nasal blocking in the probiotics group (P = 0.101). Concomitantly, fewer subjects in the probiotic group had infiltration of eosinophils in the nasal mucosa compared to the placebo group, 57.1% vs 95% (P = 0.013). Eye symptoms tended to be slightly more frequent in the probiotic group, 12.5 d [interquartile range (IQR) 6-18] vs 7.5 d (IQR 0-11.5) (P = 0.066) during May. Fecal IgA was increased in the placebo group during the pollen season; this increase was prevented by the probiotics (P = 0.028).ConclusionBirch pollen allergy was shown to be associated with changes in fecal microbiota composition. The specific combination of probiotics used was shown to prevent the pollen-induced infiltration of eosinophils into the nasal mucosa, and indicated a trend for reduced nasal symptoms.

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Novel birch pollen specific immunotherapy formulation based on contiguous overlapping peptides.

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Novel birch pollen specific immunotherapy formulation based on contiguous overlapping peptides.

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