Yeast-based vaccines as immunotherapy

Abstract

Compositions and methods for treating and/or preventing a variety of diseases and conditions that are amenable to immunotherapy and, in one particular embodiment, compositions and methods for treating and/or preventing cancer in an animal are described. Specifically improvements related to the use of a yeast-based vaccine comprising a yeast vehicle and an antigen that is selected to elicit an antigen-specific cellular and humoral immune response in an animal, for use in prophylactic and/or therapeutic vaccination and the prevention and/or treatment of a variety of diseases and conditions are disclosed.

What is claimed is: 
     
         1 . A method to treat an infectious disease, comprising administering a therapeutic composition to an animal that has an infectious disease, the therapeutic composition comprising:
 a) a yeast vehicle; and   b) a fusion protein expressed by the yeast vehicle, the fusion protein comprising:
 i) at least one antigen from an infectious disease pathogen; and 
 ii) a peptide linked to the N-terminus of the antigen or immunogenic domain thereof, the peptide consisting of between two and six amino acid residues that are heterologous to the antigen or immunogenic domain thereof, wherein the peptide stabilizes the expression of the fusion protein in the yeast vehicle or prevents posttranslational modification of the expressed fusion protein, and wherein the peptide does not negatively impact an immune response against the antigen or immunogenic domain thereof; 
 wherein the first six amino acids of the fusion protein consist of an amino acid sequence of M-X 2 —X 3 —X 4 —X 5 —X 6 ; 
 wherein M is methionine; 
 wherein X 2  is any amino acid except glycine, proline, lysine or arginine; 
 wherein X 3  is any amino acid except methionine, lysine or arginine; 
 wherein X 4  is any amino acid except methionine, lysine or arginine; 
 wherein X 5  is any amino acid except methionine, lysine or arginine; and 
 wherein X 6  is any amino acid except methionine. 
   
     
     
         2 . The method of  claim 1 , wherein X 6  is a proline. 
     
     
         3 . The method of  claim 1 , wherein the peptide consists of an amino acid sequence of M-A-D-E-A-P (SEQ ID NO:1). 
     
     
         4 . The method of  claim 1 , wherein the infectious disease pathogen is selected from the group consisting of: a virus, a bacterium, a fungus, and a parasite. 
     
     
         5 . The method of  claim 1 , wherein the infectious disease pathogen is a virus. 
     
     
         6 . The method of  claim 1 , wherein the antigen is from hepatitis B virus (HBV). 
     
     
         7 . The method of  claim 1 , wherein the antigen is from hepatitis C virus (HCV). 
     
     
         8 . The method of  claim 1 , wherein the antigen is from human immunodeficiency virus (HIV). 
     
     
         9 . The method of  claim 1 , wherein the yeast vehicle is a whole, killed yeast. 
     
     
         10 . The method of  claim 1 , wherein yeast vehicle is from  Saccharomyces cerevisiae.    
     
     
         11 . The method of  claim 1 , wherein the composition further comprises a biological response modifier. 
     
     
         12 . The method of  claim 1 , wherein the composition further comprises an immunopotentiator. 
     
     
         13 . The method of  claim 1 , wherein the therapeutic composition is administered in combination with another therapeutic treatment for the infectious disease. 
     
     
         14 . The method of  claim 1 , wherein the therapeutic composition is administered to the animal every two weeks. 
     
     
         15 . The method of  claim 1 , wherein the therapeutic composition is administered to the animal from about one to about 4 times over a time period of from about 1 month to about 6 months. 
     
     
         16 . The method of  claim 1 , wherein the therapeutic composition is administered by subcutaneous injection. 
     
     
         17 . A method to treat an infectious disease, comprising administering a composition to an animal that has an infectious disease, the composition comprising:
 a) a yeast vehicle; and   b) a fusion protein expressed by the yeast vehicle, the fusion protein comprising:
 i) at least one antigen from an infectious disease pathogen; and 
 ii) a peptide linked to the N-terminus of the antigen or immunogenic domain thereof, the peptide consisting of between two and six amino acid residues that are heterologous to the antigen or immunogenic domain thereof, wherein the peptide stabilizes the expression of the fusion protein in the yeast vehicle or prevents posttranslational modification of the expressed fusion protein; 
 wherein the amino acid residue at position one of the fusion protein is a methionine; 
 wherein the amino acid residue at position two of the fusion protein is not a glycine or a proline; 
 wherein none of the amino acid residues at positions 2-6 of the fusion protein is a methionine; and, 
 wherein none of the amino acid residues at positions 2-5 of the fusion protein is a lysine or an arginine. 
   
     
     
         18 . The method of  claim 17 , wherein the peptide consists of six amino acid residues that are heterologous to the antigen. 
     
     
         19 . The method of  claim 17 , wherein the infectious disease pathogen is selected from the group consisting of: a virus, a bacterium, a fungus, and a parasite. 
     
     
         20 . The method of  claim 17 , wherein the infectious disease pathogen is a virus.