title: 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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01719133.
authors.affiliation: Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV), Rue du Bugnon, Lausanne, 1011, Switzerland. francois.spertini@chuv.ch.
authors.forename: Céline
authors.initials: C
authors.lastname: Pellaton
authors.forename: Yannick
authors.initials: Y
authors.lastname: Perrin
authors.forename: Caroline
authors.initials: C
authors.lastname: Boudousquié
authors.forename: Nathalie
authors.initials: N
authors.lastname: Barbier
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Wassenberg
authors.forename: Giampietro
authors.initials: G
authors.lastname: Corradin
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Thierry
authors.forename: Régine
authors.initials: R
authors.lastname: Audran
authors.forename: Christophe
authors.initials: C
authors.lastname: Reymond
authors.forename: François
authors.initials: F
authors.lastname: Spertini