Mimotope and anti-idiotypic vaccines to induce an anti-IgE response.
We have defined epitopes on human IgE by screening different phage display random peptide libraries with a monoclonal anti-IgE antibody termed BSW17. The selected mimotopes and epitopes within the Cepsilon3 and Cepsilon4 region of IgE induced antibodies that were nonanaphylactogenic and had biological activity similar to BSW17. The chemically synthesized and KLH-coupled IgE epitopes or mimotopes were used to induce an anti-IgE response in rhesus monkeys. The immunized rhesus monkeys were subsequently protected in a PCA test when sensitized with human IgE and triggered with the corresponding allergen. Furthermore, using the same monoclonal anti-IgE antibody, we also generated an anti-idiotypic antibody that showed sequence homology with the IgE epitope in the Cepsilon3 domain. This anti-idiotypic antibody as well as the mimotopes were then used in a mouse model to induce orally an anti-IgE immune response. For this purpose mice were fed by intragastric gavages with bacteriophages displaying the small IgE-homologous structures. Orally immunized mice produced serum anti-IgE antibodies that were inhibited by BSW17 suggesting that it may be possible to induce a systemic anti-IgE response orally.
Stadler
B M
BM
Institute of Immunology and Allergology, Inselspital, University of Bern, Switzerland. beda.stadler@insel.ch
Zürcher
A W
AW
Miescher
S
S
Kricek
F
F
Vogel
M
M
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D018604:Epitope Mapping; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000517:prevention & control; D007073:Immunoglobulin E / Q000276:immunology*; D051379:Mice; D019151:Peptide Library; D011994:Recombinant Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D019151:Peptide Library; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D007073:Immunoglobulin E