US2004141993A1PendingUtilityA1

Synthetic peptide composition as immunogens for prevention of urinary tract infection

62
Priority: Dec 22, 2000Filed: Feb 27, 2004Published: Jul 22, 2004
Est. expiryDec 22, 2020(expired)· nominal 20-yr term from priority
Inventors:Chang Yi Wang
A61K 38/00C07K 2319/00C07K 14/245A61P 13/00C07K 14/7055
62
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Claims

Abstract

The invention provides a peptide immunogen comprising a FAFSD target peptide or an anlogue thereof, covalently linked to a helper T cell epitope and optionally to an invasin immunostimulatory domain. The present invention also provides for the use of such peptide immunogens to elicit the production in mammals of high titer polyclonal antibodies, which are specific to the FAFSD target peptide. The peptide immunogens are expected to be useful in evoking antibodies that prevent the adherence of E. coli and other enterobacteria to the mucosa for protection against urinary tract infection.

Claims

exact text as granted — not AI-modified
We claim:  
     
         1 . A FAFSD target peptide selected from the group consisting of SEQ ID NOS: 3, 6, 8, and a crossreactive and immunologically functional analogue thereof and mimetopes thereof.  
     
     
         2 . A FAFSD target peptide according to  claim 1  wherein the a crossreactive and immunologically functional analogue is selected from the group consisting of SEQ ID NOs: 4, 5, 86, 86 and 88.  
     
     
         3 . A peptide immunogen comprising a helper T cell epitope sequence (Th) covalently attached to a FAFSD target peptide comprising no more than 30 amino acids of the carbohydrate binding pocket of FimH, or a crossreactive and immunologically functional analogue thereof, or a mimetope thereof.  
     
     
         4 . A peptide immunogen according to  claim 3  wherein the crossreactive and immunologically functional analogue is selected from the group consisting of SEQ ID NOs: 4, 5, 86, 86 and 88.  
     
     
         5 . A peptide immunogen comprising a carrier protein covalently attached to a FAFSD target peptide comprising no more than 30 amino acids of the carbohydrate binding pocket of FimH, or a crossreactive and immunologically functional analog thereof, or a mimetope thereof.  
     
     
         6 . A peptide immunogen according to  claim 5  wherein the crossreactive and immunologically functional analogue is selected from the group consisting of SEQ ID NOs: 4, 5, 86, 86 and 88.  
     
     
         7 . A peptide immunogen of  claim 3  wherein the FAFSD target peptide is cyclized.  
     
     
         8 . A peptide immunogen of  claim 4  wherein the FAFSD target peptide is cyclized.  
     
     
         9 . A peptide immunogen of  claim 5  wherein the FAFSD target peptide is cyclized.  
     
     
         10 . A peptide immunogen of  claim 6  wherein the FAFSD target peptide is cyclized.  
     
     
         11 . A peptide immunogen represented by the formulas 
       (A) n -(FAFSD peptide)-(B) o -(Th) m -Xor(A) n -(Th) m -(B) o -(FAFSD peptide)-Xor(FAFSD peptide)-(B) o -(Th) m -(A) n -Xor(Th) m -(B) o -(FAFSD peptide)-(A) n -X wherein    each A is independently an amino acid or an invasin domain;    each B is independently an amino acid or a chemical linker chosen from the group consisting of: amino acids, gly-gly, (α, ε-N) Lys, Pro-Pro-Xaa-Pro-Xaa-Pro (SEQ ID NO:73); NHCH(X)CH 2 SCH 2 CO—, —NHCH(X)CH 2 SCH 2 CO(ε-N)Lys-, —NHCH(X)CH 2 S-succinimidyl(ε-N)Lys-, and —NHCH(X)CH 2 S-(succinimidyl)-;    each Th is independently a sequence of amino acids that constitutes a helper T cell epitope, or an immune enhancing analog or segment thereof;    (FAFSD peptide) a FAFSD target peptide as defined in  claim 1;     X is α-COOH or α-CONH 2 ;    n is from 0 to about 10;    m is from 1 to about 4; and    o is from 0 to about 10.    
     
     
         12 . A peptide immunogen of  claim 11 , wherein B is an amino acid selected from the group consisting of natural and unnatural amino acids.  
     
     
         13 . A peptide immunogen of claims  3  wherein said Th is a combinatorial Th epitope library.  
     
     
         14 . A peptide immunogen of claims  4  wherein said Th is a combinatorial Th epitope library.  
     
     
         15 . A peptide immunogen of claims  5  wherein said Th is a combinatorial Th epitope library.  
     
     
         16 . A peptide immunogen of claims  6  wherein said Th is a combinatorial Th epitope library.  
     
     
         17 . A peptide immunogen of claims  11  wherein said Th is a combinatorial Th epitope library.  
     
     
         18 . A peptide immunogen of  claim 3  wherein said Th has an amino acid sequence selected from the group consisting of SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NOS:38-39, and SEQ ID NOS:49-50, and SEQ ID NO:67.  
     
     
         19 . A peptide immunogen of  claim 4  wherein said Th has an amino acid sequence selected from the group consisting of SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NOS:38-39, and SEQ ID NOS:49-50, and SEQ ID NO:67.  
     
     
         20 . A peptide immunogen of  claim 5  wherein said Th has an amino acid sequence selected from the group consisting of SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NOS:38-39, and SEQ ID NOS:49-50, and SEQ ID NO:67.  
     
     
         21 . A peptide immunogen of claims  6  wherein said Th has an amino acid sequence selected from the group consisting of SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NOS:38-39, and SEQ ID NOS:49-50, and SEQ ID NO:67.  
     
     
         22 . A peptide immunogen of  claim 11  wherein said Th has an amino acid sequence selected from the group consisting of SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NOS:38-39, and SEQ ID NOS:49-50, and SEQ ID NO:67.  
     
     
         23 . A peptide immunogen of  claim 11  wherein said peptide immunogen has an amino acid sequence selected from the group consisting of SEQ ID NOs:74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84 and 85.  
     
     
         24 . A peptide immunogen of  claim 11  wherein at least one A is an invasin domain.  
     
     
         25 . A peptide immunogen of  claim 11  wherein n is 3, and (A) 3  is (invasin domain)-Gly-Gly.  
     
     
         26 . A peptide immunogen of  claim 24  or  claim 25  wherein said invasin domain has the amino acid sequence of SEQ ID NO:72.  
     
     
         27 . A synthetic peptide of about 20 to about 100 amino acids, which comprises the amino acid sequences of 
 (a) an invasin domain,    (b) a helper T cell (Th) epitope, and    (c) a FAFSD target peptide comprising no more than 30 amino acids of the carbohydrate binding pocket of FimH, or a crossreactive and immunologically functional analog thereof, or a mimetope thereof.    
     
     
         28 . A synthetic peptide of  claim 27  of about 25 to 80 amino acids.  
     
     
         29 . A synthetic peptide of  claim 27  of about 25 to 65 amino acids.  
     
     
         30 . A pharmaceutical composition comprising an immunologically effective amount of a target peptide immunogen of claims  3 ,  4 ,  5 ,  6 ,  7 ,  8 ,  9 ,  10 ,  11 ,  12 ,  13 ,  14 ,  15 ,  16 ,  17 ,  18 ,  19 ,  20 ,  21 ,  22 ,  23 ,  24 ,  25 ,  27 ,  28 , or  29  and a pharmaceutically acceptable vaccine delivery vehicle.  
     
     
         31 . A pharmaceutical composition comprising an immunologically effective amount of a target peptide immunogen of  claim 26 , and a pharmaceutically acceptable vaccine delivery vehicle.  
     
     
         32 . A pharmaceutical composition of  claim 30 , wherein said immunologically effective amount of said peptide or peptide conjugate is about 0.25 μg to about 1 mg per kilogram body weight per dose.  
     
     
         33 . A pharmaceutical composition of  claim 31 , wherein said immunologically effective amount of said peptide or peptide conjugate is about 0.25 μg to about 1 mg per kilogram body weight per dose.  
     
     
         34 . A method for inducing anti-FAFSD peptide antibody production in a mammal by administering to said mammal a pharmaceutical composition of  claim 30 .  
     
     
         35 . A method for inducing anti-FAFSD peptide antibody production in a mammal by administering to said mammal a pharmaceutical composition of  claim 31 .  
     
     
         36 . A method for inducing anti-FAFSD peptide antibody production in a mammal by administering to said mammal a pharmaceutical composition of  claim 32 .  
     
     
         37 . A method for inducing anti-FAFSD peptide antibody production in a mammal by administering to said mammal a pharmaceutical composition of  claim 33 .  
     
     
         38 . A method for reducing adherence to the urinary tract mucosa of a mammal by type 1 fimbriated uropathogenic enterobacteriae to prevent urinary tract infection by administering to the mammal a pharmaceutical composition of  claim 30 .  
     
     
         39 . A method for reducing adherence to the urinary tract mucosa of a mammal by type 1 fimbriated uropathogenic enterobacteriae to prevent urinary tract infection by administering to the mammal a pharmaceutical composition of  claim 31 .  
     
     
         40 . A method for reducing adherence to the urinary tract mucosa of a mammal by type 1 fimbriated uropathogenic enterobacteriae to prevent urinary tract infection by administering to the mammal a pharmaceutical composition of  claim 32 .  
     
     
         41 . A method for reducing adherence to the urinary tract mucosa of a mammal by type 1 fimbriated uropathogenic enterobacteriae to prevent urinary tract infection by administering to the mammal a pharmaceutical composition of  claim 33 .  
     
     
         42 . A method according to  claim 34  wherein the enterobacteriae is  E. coli.    
     
     
         43 . A method according to  claim 35  wherein the enterobacteriae is  E. coli.    
     
     
         44 . A method according to  claim 36  wherein the enterobacteriae is  E. coli.    
     
     
         45 . A method according to  claim 37  wherein the enterobacteriae is  E. coli.    
     
     
         46 . A polymer of at least two FAFSD peptides of  claim 1  cross-linked by a bifunctional crosslinking agent.  
     
     
         47 . A polymer of at least two FAFSD peptides of  claim 2  cross-linked by a bifunctional crosslinking agent.  
     
     
         48 . A polymer of at least two FAFSD peptide immunogens of  claim 3  cross-linked by a bifunctional crosslinking agent.  
     
     
         49 . A polymer of at least two FAFSD peptide immunogens of  claim 4  cross-linked by a bifunctional crosslinking agent.  
     
     
         50 . A polymer of at least two FAFSD peptide immunogens of  claim 5  cross-linked by a bifunctional crosslinking agent.  
     
     
         51 . A polymer of at least two FAFSD peptide immunogens of  claim 6  cross-linked by a bifunctional crosslinking agent.

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