|
| Article Authors: | Margitta Worm; Hae-Hyuk Lee; Jörg Kleine-Tebbe; Roderick P Hafner; Paul Laidler; David Healey; Cecile Buhot; Adrienne Verhoef; Bernard Maillère; A Barry Kay; Mark Larché |
|---|
| Article Title: | Development and preliminary clinical evaluation of a peptide immunotherapy vaccine for cat allergy. |
|---|
|
| Reference ID: | 1021468 |
|---|
| Abstract: | BACKGROUND: Allergic sensitization to cat allergens is common and represents a major risk factor for asthma. Specific immunotherapy (SIT) is effective but cumbersome and associated with IgE-dependent adverse events. Immunotherapy targeting allergen-specific T cells, with synthetic peptides representing T-cell epitopes, might improve safety and reduce the duration of treatment. OBJECTIVE: We sought to define major T-cell epitopes of Fel d 1 for peptide immunotherapy, generate a peptide vaccine, and evaluate its safety and tolerability in subjects with cat allergy. METHODS: We determined the binding affinities of Fel d 1 peptides for 10 commonly expressed HLA-DR molecules. Functionally immunodominant peptides were identified by means of proliferation and cytokine secretion. Histamine-releasing activity was assessed, and a peptide vaccine was formulated. Safety and tolerability were evaluated in a dose-ranging phase IIa clinical trial. RESULTS: MHC-binding sequences were identified throughout Fel d 1. Some regions contained multiple overlapping T-cell epitopes that bound multiple MHC molecules. Immunodominant sequences were identified on the basis of proliferative and cytokine (IFN-, IL-10, and IL-13) responses. Cat allergen extract, but not peptides, induced histamine release in blood basophils. A single administration of peptide vaccine was safe and well tolerated. The dose of vaccine resulting in the greatest inhibition of the late-phase skin response to intradermal whole allergen challenge was 3 nmol. CONCLUSIONS: Fel d 1 contains multiple overlapping MHC-binding motifs. A peptide vaccine comprising the immunodominant regions of the allergen was safe and well tolerated when given to subjects with cat allergy as a single dose. The dose of vaccine resulting in the greatest reduction in late-phase skin response was defined for future clinical development. |
|---|
| Affiliations: | Department of Dermatology, Venerology and Allergology, Charité Universitätsmedizin, Berlin, Germany. |
|---|
| Date: | 2011 |
|---|
| Reference Type: | Literature |
|---|
| PubMed ID: | 21211644 |
|---|
| Journal: | J Allergy Clin Immunol |
|---|
| Journal Volume: | 127 |
|---|
| Article Pages: | 89-97, 97.e1-14 |
|---|
| Journal ISSN: | 1097-6825 |
|---|
| Article Chemical List: | Epitopes, T-Lymphocyte;Fel d 1 protein, Felis domesticus;Glycoproteins;HLA-DR Antigens;Immunodominant Epitopes;Vaccines, Subunit |
|---|
| Article MeSH List: | Amino Acid Sequence; Animals; Cats; Double-Blind Method; Epitopes, T-Lymphocyte(immunology); Glycoproteins(immunology; therapeutic use); HLA-DR Antigens; Humans; Hypersensitivity(immunology; prevention & control); Immunodominant Epitopes; Immunotherapy(methods); Molecular Sequence Data; Vaccines, Subunit(immunology; therapeutic use) |
|---|
| Curation Last Updated: | 2013-05-28 22:23:33 |
|---|
