A hypoallergenic cat vaccine based on Fel d 1-derived peptides fused to hepatitis B PreS.

Abstract

BACKGROUND:

Allergen-specific immunotherapy is clinically effective for the treatment of cat allergy but shows a high rate of side effects.

OBJECTIVE:

We sought to engineer recombinant fusion proteins for cat immunotherapy that allow reducing both IgE-mediated and T cell-mediated side effects.

METHODS:

Fusion proteins consisting of the hepatitis B virus-derived PreS domain and 2 nonallergenic Fel d 1-derived peptides were expressed in Escherichia coli and purified. IgE reactivity and allergenic activity of Fel d 1 and the fusion proteins were compared by using IgE-binding assays and basophil activation tests in patients with cat allergy. Mice and rabbits were immunized subcutaneously with Fel d 1 and the fusion proteins to investigate the allergenicity of the vaccines and the development of Fel d 1-specific IgG antibodies.

RESULTS:

The recombinant fusion proteins showed no relevant IgE reactivity and exhibited more than 1000-fold reduced allergenic activity in basophil activation tests. On immunization of mice and rabbits, the fusion proteins induced Fel d 1-specific IgG antibodies that inhibited the binding of allergic patients' IgE to the allergen without allergic sensitization to Fel d 1.

CONCLUSION:

The described recombinant fusion proteins exhibit strongly reduced IgE-mediated allergenic activity, contain less than 40% of the Fel d 1 sequence, and thus lack many of the specific T-cell epitopes. Therefore they should represent safe vaccines for the treatment of cat allergy.

• Authors: Katarzyna Niespodziana, Margarete Focke-Tejkl, Birgit Linhart, Vera Civaj, Katharina Blatt, Peter Valent, Marianne van Hage, Hans Grönlund, Rudolf Valenta
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 127 Issue 6 Pg. 1562-70.e6 (Jun 2011) ISSN: 1097-6825 [Electronic] United States
• PMID: 21411130 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Chemical References

• Allergens
• ENPP3 protein, human
• Glycoproteins
• Hepatitis B Surface Antigens
• Immunoglobulin G
• Recombinant Fusion Proteins
• Vaccines, Synthetic
• Immunoglobulin E
• Phosphoric Diester Hydrolases
• Pyrophosphatases
• Fel d 1 protein, Felis domesticus

Topics

• Allergens (chemistry, genetics, immunology)
• Amino Acid Sequence
• Animals
• Basophils (immunology)
• Case-Control Studies
• Cats
• Desensitization, Immunologic (methods)
• Glycoproteins (chemistry, genetics, immunology)
• Hepatitis B Surface Antigens (chemistry, genetics, immunology)
• Humans
• Hypersensitivity (immunology, therapy)
• Immunoglobulin E (metabolism)
• Immunoglobulin G (biosynthesis)
• Mice
• Molecular Sequence Data
• Pets (immunology)
• Phosphoric Diester Hydrolases (metabolism)
• Protein Conformation
• Protein Engineering
• Pyrophosphatases (metabolism)
• Rabbits
• Rats
• Recombinant Fusion Proteins (chemistry, genetics, immunology)
• T-Lymphocytes (immunology)
• Vaccines, Synthetic (chemistry, genetics, immunology)