Compositions and methods for treatment of celiac disease

Abstract

The invention provides agents and vaccines for treating and diagnosing celiac disease. In particular, the present invention provides a combination of three peptides that are useful for treating and diagnosing celiac disease in a large proportion of patients.

1 . An agent comprising
 i) a first peptide comprising the amino acid sequence LQPFPQPELPYPQPQ (SEQ ID NO: 13), or a biologically active fragment or variant thereof,   ii) a second peptide comprising the amino acid sequence QPFPQPEQPFPWQP (SEQ ID NO: 14), or a biologically active fragment or variant thereof, and   iii) a third peptide comprising the amino acid sequence PEQPIPEQPQPYPQQ (SEQ ID NO: 16), or a biologically active fragment or variant thereof.   
     
     
         2 . The agent of  claim 1 , wherein the second peptide comprises the amino acid sequence PQQPFPQPEQPFPWQP (SEQ ID NO:320), or a biologically active fragment or variant thereof, and/or the third peptide comprises the amino acid sequence FPEQPIPEQPQPYPQQ (SEQ ID NO:321), or a biologically active fragment or variant thereof. 
     
     
         3 . The agent of  claim 1 , wherein the first, second and/or third peptides comprise an N terminal acetyl group or pyroglutamate group, and/or a C terminal amide group. 
     
     
         4 . The agent of  claim 3 , wherein the first, second and/or third peptides comprise an N terminal pyroglutamate group and a C terminal amide group. 
     
     
         5 . The agent of  claim 1 , wherein the first, second and/or third peptides are conjugated to a compound. 
     
     
         6 . The agent of  claim 5 , wherein the compound is an adjuvant, or an MHC molecule or binding fragment thereof. 
     
     
         7 . The agent of  claim 1 , wherein two or three of the first, second and third peptides, or the biologically active fragment or variant of one or more thereof, are on a single polypeptide chain. 
     
     
         8 . The agent of  claim 1  comprising one or more additional peptides comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:47, 48, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 75, 76, 77, 78, 79, 80, 81, 89, 90, 91, 92, 95, 102, 103, 104, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 136, 169, 170, 171, 172, 173, 174, 177, 178, 179, 180, 183, 184, 187, 188, 189, 190, 191, 192, 209, 210, or a biologically active fragment or variant of any one or more thereof. 
     
     
         9 . An agent comprising one or more polynucleotides encoding the agent of  claim 1 . 
     
     
         10 . An agent comprising
 i) a first peptide as defined in  claim 1  or a polynucleotide therefor,   ii) a second peptide as defined in  claim 1  or a polynucleotide therefor, and   iii) a third peptide as defined in  claim 1  or a polynucleotide therefor.   
     
     
         11 . A substantially purified and/or recombinant peptide comprising an amino acid sequence as shown in any one or more of SEQ ID NO:16, 69, 73, 75, 78, 80, 87, 91, 92, 95, 96, 98, 100, 104, 107, 113, 116, 117, 123, 138, 144, 147, 149, 153, 155, 156, 159, 161, 163, 165, 179, 181, 185, 187, 189, 195, 196, 198, 202, 204, 205, 207, 209, 215, 223, or a biologically active fragment or variant of any one or more thereof. 
     
     
         12 . An isolated and/or exogenous polynucleotide encoding at least one peptide of  claim 11 . 
     
     
         13 . A vaccine comprising the agent of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         14 . (canceled) 
     
     
         15 . An isolated antigen presenting cell comprising the agent of  claim 1 . 
     
     
         16 . (canceled) 
     
     
         17 . A method of modulating a T cell response to a gluten peptide, inducing immune tolerance to a gluten peptide, treating celiac disease, or modifying cytokine secretion in a subject who is sensitive to gluten, the method comprising administering to the subject an effective amount of the agent of  claim 1 . 
     
     
         18 .- 23 . (canceled) 
     
     
         24 . A method for diagnosing celiac disease in a subject, the method comprising contacting a sample from the subject with the agent of  claim 1 , and determining in vitro whether one or more of the peptides bind T cells in the sample, wherein the binding of one or more of the peptides to T cells indicates that the subject has, or is susceptible to, celiac disease. 
     
     
         25 .- 26 . (canceled) 
     
     
         27 . A kit comprising the agent of  claim 1 , and means to detect binding of one or more of the peptides to T cells. 
     
     
         28 . A method for producing an antigen presenting cell, the method comprising
 i) obtaining an antigen presenting cell, and   ii) contacting the cell in vitro with the agent of  claim 1 .   
     
     
         29 .- 32 . (canceled) 
     
     
         33 . A method for improving the half life and/or bioavailability of a peptide when administered to a subject, the method comprising modifying the N terminus of the peptide to include an N terminal acetyl or pyroglutamate and modifying the C terminus of the peptide to include a C terminal amide. 
     
     
         34 . The method of  claim 33  in which the peptide is for administering to a subject to induce immune tolerance.