Non-Anaphylactogenic IgE Fusion Proteins

Abstract

The present invention provides compositions and methods for the use of antigenic peptides derived from the Fc portion of the epsilon heavy chain of IgE molecules from two unrelated species as vaccines for the treatment and prevention of IgE-mediated allergic disorders, in particular, the invention provides compositions for the treatment and prevention of IgE-mediated allergic disorders comprising an immunogenic amount of one or more antigenic peptides.

1 . An isolated antigenic peptide comprising: (i) amino acid residues of a CH3domain of an IgE molecule from a first species; (ii) amino acid residues of a CH3 domain of an IgE molecule of a second unrelated species, wherein the amino acid residues of the CH3 domain of the IgE molecule from the first species are conserved in the CH3 domain of the IgE molecule of the second species, the amino acid residues of the CH3 domain of the IgE molecule from the second species are not conserved in the CH3 domain of the IgE molecule of the first species, and the antigenic peptide induces an anti-IgE immune response that does not cause anaphylaxis when administered to an animal. 
     
     
         2 . The antigenic peptide of  claim 1  comprising at least 10 amino acid residues of the CH3 domain of the IgE molecule from either the first or second species. 
     
     
         3 . The antigenic peptide of  claim 1  comprising at least 10 amino acid residues of the CH3 domain of the IgE molecule from the first species and at least 10 amino acid residues of the CH3 domain of the IgE molecule from the second species. 
     
     
         4 . The antigenic peptide of  claim 1  comprising a total of between about 28 and about 31 amino acid residues of the CH3 domain of the IgE molecule from the first species and the CH3 domain of the IgE molecule from the second species. 
     
     
         5 .- 6 . (canceled) 
     
     
         7 . An isolated antigenic fusion protein comprising amino acid residues of a CH3 domain of an IgE molecule from a first species flanked by amino acid residues of a CH3domain of an IgE molecule of a second unrelated species, wherein the amino acid residues of the CH3 domain of the IgE molecule from the first species are conserved in the CH3 domain of the IgE molecule of the second species, the amino acid residues of the CH3 domain of the IgE molecule from the second species are not conserved in the CH3 domain of the IgE molecule of the first species, and a heterologous protein carrier, wherein the antigenic fusion protein induces an anti-IgE immune response that does not cause anaphylaxis when administered to an animal. 
     
     
         8 . (canceled) 
     
     
         9 . An isolated peptide comprising an amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9. 
     
     
         10 . The isolated antigenic fusion protein of  claim 7  wherein the heterologous protein carrier comprises the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9. 
     
     
         11 - 18 . (canceled) 
     
     
         19 . A pharmaceutical composition for inducing an anti-IgE immune response that does not cause anaphylaxis, comprising one or more antigenic peptides having an amino acid sequence comprising amino acid residues of a CH3 domain of an IgE molecule or a fragment thereof species and a pharmaceutically acceptable carrier. 
     
     
         20 . The pharmaceutical composition of  claim 19 , wherein at least one antigenic peptide has the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. 
     
     
         21 . A pharmaceutical composition for inducing an anti-IgE immune response that does not cause anaphylaxis comprising one or more antigenic fusion proteins having an amino acid sequence comprising amino acid residues of a CH3 domain of an IgE molecule or a fragment thereof, a heterologous carrier protein and a pharmaceutically acceptable carrier. 
     
     
         22 . The pharmaceutical composition of  claim 20 , wherein at least one antigenic fusion protein has the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. 
     
     
         23 . The pharmaceutical composition of  claim 21 , wherein the heterologous carrier protein is selected from the group consisting of KLH, PhoE, rmLT, TraT, gD from BHV-1 virus, SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9. 
     
     
         24 . The pharmaceutical composition of  claim 20 , further comprising an adjuvant. 
     
     
         25 . The pharmaceutical composition of  claim 20 , wherein the anti-IgE immune response is the production of anti-IgE antibodies which bind to soluble IgE in serum and other bodily fluids, prevent IgE from binding to its high affinity receptors on mast cells and basophils, and do not cross-link receptor-bound IgE. 
     
     
         26 .- 42 . (canceled) 
     
     
         43 . The pharmaceutical composition of  claim 21 , further comprising an adjuvant.