Toll-like receptor 5 ligands and methods of use

Abstract

The invention provides an immunomodulatory flagellin peptide having at least about 10 amino acids of substantially the amino acid sequence GAVQNRFNSAIT, or a modification thereof, and having toll-like receptor 5 (TLR5) binding. Methods of inducing an immune response are also provided.

1 - 35 . (canceled) 
     
     
         36 . A method of inducing an antigen-specific immune response in an individual,
 said method comprising administering to said individual an immunogenic amount of an immunogenic composition, said immunogenic composition comprising an antigen and a flagellin peptide that stimulates TLR5 which peptide consists of the conserved regions of a naturally occurring flagellin protein or a TLR5 stimulatory portion of said conserved regions, wherein said conserved regions are defined as sequences that align with consensus sequence SEQ ID NO:34.   
     
     
         37 . The method of  claim 36 , wherein said antigen and said flagellin peptide form a chimeric polypeptide. 
     
     
         38 . The method of  claim 36 , wherein said antigen is coupled to the flagellin peptide. 
     
     
         39 . The method of  claim 36 , wherein said antigen is selected from the group consisting of polypeptides, polysaccharides, pathologically aberrant cells and bacteria. 
     
     
         40 . The method of  claim 36 , wherein said flagellin peptide further comprises an ADCC targeting molecule. 
     
     
         41 . A flagellin peptide that stimulates TLR5, which peptide consists of the conserved regions of a naturally occurring flagellin protein or a TLR5 stimulatory portion of said conserved regions, wherein said conserved regions are defined as sequences that align with consensus sequence SEQ ID NO:34; and wherein said peptide coupled to an antigen or to a heterologous moiety. 
     
     
         42 . The method of  claim 41 , wherein said heterologous moiety is an antibody-dependent cell cytotoxicity (ADCC) targeting moiety. 
     
     
         43 . The peptide of  claim 41 , wherein the heterologous moiety is a targeting moiety or facilitates detection, facilitates purification, or enhances immunostimulation activity of TLR5. 
     
     
         44 . The peptide of  claim 41 , wherein the heterologous moiety is a cytokine. 
     
     
         45 . The peptide of  claim 44 , wherein the cytokine is TNFα, IL-1 or IL-6. 
     
     
         46 . The peptide of  claim 41 , wherein the heterologous moiety is an antigen. 
     
     
         47 . The method of  claim 46 , wherein the antigen is selected from the group consisting of polypeptides, polysaccharides, pathologically aberrant cells and bacteria. 
     
     
         48 . A method of stimulating a TLR5 dependent immune response in an individual having a pathological condition which method comprises administering to said individual an effective amount of the peptide of  claim 41 . 
     
     
         49 . A method of stimulating a TLR5-dependent immune response in an individual having a pathological condition,
 said method comprising administering to said individual a combination of the peptide of  claim 41  along with an additional immunomodulatory molecule.   
     
     
         50 . The method of  claim 49 , wherein said additional immunomodulatory molecule is an antibody, cytokine or growth factor. 
     
     
         51 . A method of stimulating a TLR5-dependent immune response in an individual having a pathological condition,
 said method comprising administering to said individual a combination of the peptide of  claim 42  along with an additional immunomodulatory molecule.   
     
     
         52 . The method of  claim 49 , wherein said pathological condition is selected from the group consisting of proliferative disease, autoimmune disease, infectious disease and inflammatory disease.