Analysis of epitope-specific immune responses induced by vaccination with structurally folded and unfolded recombinant Bet v 1 allergen derivatives in man.
Previously, we have constructed recombinant derivatives of the major birch pollen allergen, Bet v 1, with a more than 100-fold reduced ability to induce IgE-mediated allergic reactions. These derivatives differed from each other because the two recombinant Bet v 1 fragments represented unfolded molecules whereas the recombinant trimer resembled most of the structural fold of the Bet v 1 allergen. In this study, we analyzed the Ab (IgE, IgG subclass, IgA, IgM) response to Bet v 1, recombinant and synthetic Bet v 1-derived peptides in birch pollen allergic patients who had been vaccinated with the derivatives or adjuvant alone. Furthermore, we studied the induction of IgE-mediated skin responses in these patients using Bet v 1 and Bet v 1 fragments. Both types of vaccines induced a comparable IgG1 and IgG4 response against new sequential epitopes which overlap with the conformational IgE epitopes of Bet v 1. This response was 4- to 5-fold higher than that induced by immunotherapy with birch pollen extract. Trimer more than fragments induced also IgE responses against new epitopes and a transient increase in skin sensitivity to the fragments at the beginning of therapy. However, skin reactions to Bet v 1 tended to decrease one year after treatment in both actively treated groups. We demonstrate that vaccination with folded and unfolded recombinant allergen derivatives induces IgG Abs against new epitopes. These data may be important for the development of therapeutic as well as prophylactic vaccines based on recombinant allergens.
Pree
Ines
I
Department of Otolaryngology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
Reisinger
Jürgen
J
Focke
Margit
M
Vrtala
Susanne
S
Pauli
Gabrielle
G
van Hage
Marianne
M
Cromwell
Oliver
O
Gadermaier
Elisabeth
E
Egger
Cornelia
C
Reider
Norbert
N
Horak
Friedrich
F
Valenta
Rudolf
R
Niederberger
Verena
V
D000485:Allergens / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D029662:Betula / Q000235:genetics / Q000276:immunology*; D004311:Double-Blind Method; D000939:Epitopes / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007428:Intradermal Tests; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D011058:Pollen / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015202:Protein Engineering; D017510:Protein Folding; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*
D000485:Allergens; D000939:Epitopes; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; D007073:Immunoglobulin E