Polyionic papilloma virus-like particle (vlp) vaccines

Abstract

The present invention relates to the field of vaccines. In particular, the present invention provides compositions and methods relating to virus-like particle (VLP) vaccines. In one embodiment, a chimeric papillomavirus virus-like particle (VLP) comprises the L1 protein, wherein the HI loop of the L1 protein comprises negatively charged amino acids. In a more specific embodiment, a chimeric bovine papillomavirus VLP comprises the L1 protein, wherein the amino acid sequence EEEEEEEEC is inserted into the HI loop of the L1 protein.

We claim: 
     
         1 . A vaccine comprising: (a) a chimeric papillomavirus virus-like particle (VLP) comprising a L1 protein, wherein a polycationic:cysteine amino acid sequence is inserted into the HI loop of the L1 protein; and (b) a target antigen, wherein the target antigen comprises a region of negatively charged amino acids, and wherein the polycationic:cysteine amino acid sequence of the HI loop of the L1 protein is covalently bound to the negatively charged region of the target antigen, and wherein the target antigen is not the L1 protein. 
     
     
         2 . The vaccine of  claim 1 , wherein the papillomavirus is human, bovine, equine, ovine, porcine, deer, canine, feline, or rabbit. 
     
     
         3 . The vaccine of  claim 1 , wherein the papillomavirus is bovine. 
     
     
         4 . The vaccine of  claim 1 , wherein the papillomavirus is human. 
     
     
         5 . The vaccine of  claim 1 , wherein the polycationic:cysteine amino acid sequence comprises RRRRRRRRC (SEQ ID NO:12). 
     
     
         6 . The vaccine of  claim 1 , wherein the polycationic:cysteine amino acid sequence comprises KKKKKKKKC. 
     
     
         7 . The vaccine of  claim 1 , wherein the polycationic:cysteine amino acid sequence comprises HHHHHHHHC. 
     
     
         8 . The vaccine of  claim 1 , wherein the polycationic:cysteine amino acid sequence replaces amino acids 347-355 of the HI loop of the L1 protein (SEQ ID NO:5), wherein the bovine papillomavirus is type 1 bovine papillomavirus. 
     
     
         9 . The vaccine of  claim 1 , wherein the polycationic:cysteine amino acid sequence replaces amino acids 349-353 of the HI loop of the L1 protein (SEQ ID NO:5), wherein the bovine papillomavirus is type 1 bovine papillomavirus. 
     
     
         10 . The vaccine of  claim 1 , wherein the negatively charged amino acids are glutamic acid, aspartic acid or a combination thereof. 
     
     
         11 . The vaccine of  claim 1 , wherein the region of negatively charged amino acids of the target antigen comprises EEEEEEEEC (SEQ ID NO:11). 
     
     
         12 . The vaccine of  claim 1 , wherein the target antigen is a peptide or a polypeptide. 
     
     
         13 . The vaccine of  claim 1 , wherein the target antigen is selected from the group consisting of a tumor antigen, viral antigen, bacterial antigen, fungal antigen, parasitic antigen, and a pathogenic self protein. 
     
     
         14 . The vaccine of  claim 1 , wherein the target antigen is fusion protein. 
     
     
         15 . The vaccine of  claim 1 , wherein the target antigen is MUC1 peptide. 
     
     
         16 . The vaccine of  claim 1 , wherein the target antigen is human papillomavirus 16 E7 CTL epitope amino acids 49-57. 
     
     
         17 . The vaccine of  claim 1 , wherein the target antigen is  P. falciparum  circumsporozoite NANP repeat protein B cell epitope. 
     
     
         18 . The vaccine of  claim 1 , wherein the target antigen is  P. yoellii  circumsporozoite protein CD8 T-cell epitope. 
     
     
         19 . The vaccine of  claim 1 , wherein the target antigen is Dengue virus CD8 epitope. 
     
     
         20 . The vaccine of  claim 1 , wherein the target antigen is Severe Acute Respiratory Syndrome (SARS) virus CD8 epitope. 
     
     
         21 . A method of inducing an immune response comprising administering a vaccine of  claim 1 .