Toll-like receptor 2 agonists and vaccines and uses thereof

Abstract

The present invention relates to Toll-Like Receptor 2 (TLR2) agonists, in particular, to TLR2-activating lipoproteins, and more particularly to TLR2-activating lipopeptides derived from the bacteria Bordetella pertussis . The invention further extends to the use of said TLR2-activating lipoproteins as a therapeutic or as part of a vaccine composition in the treatment and prevention of infectious diseases, cancer or allergic diseases.

1 . A method for treating or preventing a condition in a subject, wherein the method comprises:
 administering to the subject a lipoprotein obtainable from  Bordetella pertussis ;
 wherein the lipoprotein comprises an N terminal signal peptide of less than 40 amino acids in length; 
 wherein the N terminal signal peptide comprises a lipobox comprising an amino acid sequence X1, X2, X3, X4; 
 wherein X1 is selected from the group consisting of Leucine, Valine and Isoleucine; 
 wherein X2 is selected from the group consisting of Alanine, Serine, Threonine, Valine and Isoleucine; 
 wherein X3 is selected from the group consisting of Glycine, Alanine, and Serine; 
 wherein X4 is Cysteine; 
 wherein X4 is capable of being acylated; 
 wherein the lipoprotein is a Toll-like receptor 2 agonist; 
 wherein the lipoprotein is selected from the group consisting of a lipoprotein comprising the amino acid sequence of SEQ ID NO:1, a lipopeptide comprising the amino acid sequence of SEQ ID N0:13, and a lipopeptide comprising the amino acid sequence of SEQ ID NO:14; and 
 wherein the condition to be treated or prevented comprises a condition caused by a pathogen, a cancer, or an allergic disease. 
   
     
     
         2 . The method as claimed in  claim 1 , wherein the lipoprotein comprises the amino acid sequence of SEQ ID NO:1, the amino acid sequence of SEQ ID NO:13, or the amino acid sequence of SEQ ID NO:14. 
     
     
         3 . The method as claimed in  claim 1 , wherein the condition to be treated or prevented is caused by a pathogen, wherein the pathogen is a bacterium, a virus, a fungus or a parasite. 
     
     
         4 . The method as claimed in  claim 3 , wherein the pathogen is a virus. 
     
     
         5 . The method as claimed in  3 , wherein the method is a method of vaccinating the subject to induce immunity against the pathogen. 
     
     
         6 . The method as claimed in  claim 3 , wherein the method further comprises administering to the subject an antigen from the pathogen. 
     
     
         7 . The method as claimed in  claim 1 , wherein the condition to be treated or prevented comprises a cancer. 
     
     
         8 . The method as claimed in  claim 7 , wherein the method further comprises administering to the subject an antigen from a tumour cell. 
     
     
         9 . The method as claimed in  claim 7 , wherein the lipoprotein comprises the amino acid sequence of SEQ ID NO:13 or the amino acid sequence of SEQ ID NO:14. 
     
     
         10 . The method as claimed in  1 , wherein the condition to be treated or prevented comprises an allergic disease. 
     
     
         11 . The method as claimed in  claim 9 , wherein the lipoprotein comprises the amino acid sequence of SEQ ID NO:13 or the amino acid sequence of SEQ ID NO:14. 
     
     
         12 . The method as claimed in  claim 11 , wherein the method further comprises administering to the subject an allergen. 
     
     
         13 . A vaccine composition for treating or preventing a condition in a subject, wherein the vaccine composition comprises:
 a lipoprotein obtainable from  Bordetella  pertussis;
 wherein the lipoprotein comprises an N terminal signal peptide of less than 40 amino acids in length; 
 wherein the N terminal signal peptide comprises a lipobox comprising an amino acid sequence X1, X2, X3, X4; 
 wherein X1 is selected from the group consisting of Leucine, Valine and Isoleucine; 
 wherein X2 is selected from the group consisting of Alanine, Serine, Threonine, Valine and Isoleucine; 
 wherein X3 is selected from the group consisting of Glycine, Alanine, and Serine; 
 wherein X4 is Cysteine; 
 wherein X4 is capable of being acylated; 
 wherein the lipoprotein is a Toll-like receptor 2 agonist; and 
 
 wherein the lipoprotein is selected from the group consisting of a lipoprotein comprising the amino acid sequence of SEQ ID NO:1, a lipopeptide comprising the amino acid sequence of SEQ ID NO:13, and a lipopeptide comprising the amino acid sequence of SEQ ID NO:14. 
     
     
         14 . The vaccine composition as claimed in  claim 13 , wherein the condition to be treated or prevented comprises a condition caused by a pathogen, a cancer, or an allergic disease. 
     
     
         15 . The vaccine composition as claimed in  claim 13 , wherein the lipoprotein comprises the amino acid sequence of SEQ ID NO:1, the amino acid sequence of SEQ ID NO:13, or the amino acid sequence of SEQ ID N0:14. 
     
     
         16 . The vaccine composition as claimed in  claim 13 , wherein the condition to be treated or prevented is caused by a pathogen, a cancer, or an allergic disease. 
     
     
         17 . The vaccine composition as claimed in  claim 16 , wherein the condition to be treated or prevented comprises a cancer. 
     
     
         18 . The vaccine composition as claimed in  claim 17 , wherein the lipoprotein comprises the amino acid sequence of SEQ ID NO:13 or the amino acid sequence of SEQ ID NO:14. 
     
     
         19 . The vaccine composition as claimed in  claim 16 , wherein the condition to be treated or prevented comprises an allergic disease. 
     
     
         20 . The vaccine composition as claimed in  claim 19 , wherein the lipoprotein comprises the amino acid sequence of SEQ ID NO:13 or the amino acid sequence of SEQ ID NO:14.