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.

SUBMITTER: Niespodziana K 

PROVIDER: S-EPMC6624143 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature