Immunomodulatory compositions and methods for treating disease with modified host defense peptides

Abstract

Compositions and methods are provided for modulating an immune response in a vertebrate subject. Compositions and methods can comprise administering a modified host defense peptide to the vertebrate subject in an amount effective to activate the immune response in the vertebrate subject, wherein the modified host defense peptide is inverted in amino acid sequence from an amino terminus to a carboxy terminus or modified to one or more D-amino acids, or both modifications, when compared to a host defense peptide. Compositions and methods are provided which comprise administering a modified host defense peptide to the vertebrate subject in an amount effective to modify an immune response in the vertebrate subject.

What is claimed: 
     
         1 . A host defense peptide comprising a modified amino acid sequence of BAMP-28 (SEQ ID NO:1), wherein the modification comprises reversed directionality of the amino acid sequence of SEQ ID NO:1, and/or inverted chirality of one or more L-amino acids of the sequence of SEQ ID NO:1. 
     
     
         2 . The peptide of  claim 1 , wherein the modification comprises reversed directionality of the amino acid sequence of SEQ ID NO:1, and inverted chirality of one or more L-amino acids of the sequence of SEQ ID NO:1. 
     
     
         3 . The peptide of  claim 2 , wherein the modification comprises reversed directionality of the amino acid sequence of SEQ ID NO:1, and inverted chirality of the L-amino acids of the sequence of SEQ ID NO:1. 
     
     
         4 . The peptide of  claim 1 , wherein the peptide comprises an amino acid sequence with 90% sequence identity to the sequence of SEQ ID NO:2. 
     
     
         5 . The peptide of  claim 4 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:2. 
     
     
         6 . The peptide of  claim 4 , wherein the peptide consists of the amino acid sequence of SEQ ID NO:2. 
     
     
         7 . The peptide of  claim 1 , wherein the peptide has between 27 and 50 amino acids. 
     
     
         8 . The peptide of  claim 1 , wherein the peptide further comprises an additional modification, said additional modification selected from glycosylation; reduction of one or more amide bonds; methylation of one or more nitrogens; esterification of one or more carboxylic acid groups; and/or modification of the amino terminus, carboxy terminus or both amino and carboxy termini with a moiety independently selected from CH 3 CO, CH 3 (CH 2 ) n CO, C 6 H 5 CH 2 CO, NH 2 , or H 2 N(CH 2 ) n CO, wherein N=1-10. 
     
     
         9 . A fusion protein comprising the peptide of  claim 1 . 
     
     
         10 . The peptide of  claim 1 , wherein the peptide is conjugated to a carbohydrate or lipid. 
     
     
         11 . A composition comprising the peptide of  claim 1  and a pharmaceutically acceptable vehicle. 
     
     
         12 . A peptide comprising between 8 and 12 amino acids of an amino acid sequence of SEQ ID NO:2. 
     
     
         13 . The peptide of  claim 12 , wherein the peptide further comprises an additional modification, said additional modification selected from glycosylation; reduction of one or more amide bonds; methylation of one or more nitrogens; esterification of one or more carboxylic acid groups; and/or modification of the amino terminus, carboxy terminus or both amino and carboxy termini with a moiety independently selected from CH 3 CO, CH 3 (CH 2 ) n CO, C 6 H 5 CH 2 CO, NH 2 , or H 2 N(CH 2 ) n CO, wherein N=1-10. 
     
     
         14 . A fusion protein comprising the peptide of  claim 12 . 
     
     
         15 . The peptide of  claim 12 , wherein the peptide is conjugated to a carbohydrate or lipid. 
     
     
         16 . A composition comprising the peptide of  claim 12  and a pharmaceutically acceptable vehicle. 
     
     
         17 . A method of modulating an immune response in a vertebrate subject in need thereof, said method comprising administering a therapeutically effective amount of the peptide of  claim 1  to said subject. 
     
     
         18 . A method of modulating an immune response in a vertebrate subject in need thereof, said method comprising administering a therapeutically effective amount of the peptide of  claim 5  to said subject.