title: Disruption of allergenic activity of the major grass pollen allergen Phl p 2 by reassembly as a mosaic protein.
abstract: The recognition of conformational epitopes on respiratory allergens by IgE Abs is a key event in allergic inflammation. We report a molecular strategy for the conversion of allergens into vaccines with reduced allergenic activity, which is based on the reassembly of non-IgE-reactive fragments in the form of mosaic proteins. This evolution process is exemplified for timothy grass pollen-derived Phl p 2, a major allergen for more than 200 million allergic patients. In a first step, the allergen was disrupted into peptide fragments lacking IgE reactivity. cDNAs coding for these peptides were reassembled in altered order and expressed as a recombinant mosaic molecule. The mosaic molecule had lost the three-dimensional structure, the IgE reactivity, and allergenic activity of the wild-type allergen, but it induced high levels of allergen-specific IgG Abs upon immunization. These IgG Abs crossreacted with group 2 allergens from other grass species and inhibited allergic patients' IgE binding to the wild-type allergen. The mosaic strategy is a general strategy for the reduction of allergenic activity of protein allergens and can be used to convert harmful allergens into safe vaccines.
authors.affiliation: Division of Immunopathology, Department of Pathophysiology, Center of Physiology, Pathophysiology and Immunology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Nadine
authors.initials: N
authors.lastname: Mothes-Luksch
authors.forename: Sabine
authors.initials: S
authors.lastname: Stumvoll
authors.forename: Birgit
authors.initials: B
authors.lastname: Linhart
authors.forename: Margit
authors.initials: M
authors.lastname: Focke
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Krauth
authors.forename: Alexander
authors.initials: A
authors.lastname: Hauswirth
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.forename: Petra
authors.initials: P
authors.lastname: Verdino
authors.forename: Tea
authors.initials: T
authors.lastname: Pavkov
authors.forename: Walter
authors.initials: W
authors.lastname: Keller
authors.forename: Monika
authors.initials: M
authors.lastname: Grote
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003888:Desensitization, Immunologic / Q000379:methods; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D006109:Poaceae / Q000235:genetics* / Q000276:immunology; D011058:Pollen / Q000235:genetics* / Q000276:immunology; D015202:Protein Engineering; D011817:Rabbits; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000517:prevention & control; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D007074:Immunoglobulin G; C084984:PHLPII protein, Phleum pratense; D010940:Plant Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D007073:Immunoglobulin E