Synthetic peptides that bind to the hepatitis B virus core and e antigens

Abstract

The present invention relates generally to the field of virology. More particularly, the invention relates to the discovery that peptides, which bind to the Hepatitis B virus (HBV) core and e antigens, can be used to inhibit HBV infection. Embodiments concern “binding partners”, which include peptides, peptidomimetics, and chemicals that resemble these molecules that interact with HBV core and e antigens, biological complexes having HBV core and e antigens joined to said binding partners, methods of identifying such binding partners, pharmaceuticals having binding partners, and methods of treatments and prevention of HBV infection.

What is claimed is:  
     
         1 . An isolated or purified peptide comprising the formula: 
 X 1   n CZASX 2   n , wherein: 
 “X 1 ” is any amino acid  
   “C” is cysteine;    “Z” is lysine or arginine;    “A” is alanine;    “S” is serine;    “X 2 ” is any amino acid; and    “n” is an integer and, wherein said peptide is less than 50 amino acids in length and specifically binds HBcAg and/or HBeAg.    
     
     
         2 . The peptide of  claim 1 , wherein the sequence is selected from the group consisting of SEQ. ID. Nos. 1-78.  
     
     
         3 . The peptide of  claim 1 , wherein “X 1   n ” or “X 2   n ” encodes an epitope of a pathogen or a toxin.  
     
     
         4 . The peptide of  claim 1 , wherein “X n ” or “X 2   n ” encodes an epitope on a herpes simplex virus (HSV).  
     
     
         5 . The peptide of  claim 4 , wherein the epitope comprises a fragment of a peptide having the sequence of SEQ. ID. Nos. 70-76.  
     
     
         6 . A nucleic acid encoding a peptide having a sequence selected from the group consisting of SEQ. ID. No. 1-78.  
     
     
         7 . A method of making a pharmaceutical comprising: 
 identifying a binding partner that interacts with HBcAg or HBeAg having a sequence selected from the group consisting of SEQ. ID. Nos. 1-78; and    incorporating a therapeutically effective amount of said binding partner into a pharmaceutical.    
     
     
         8 . A method of treatment or prevention of HBV infection comprising: 
 identifying a subject in need of a molecule that inhibits HBV infection; and    providing said subject with a binding partner that interacts with HBcAg or HBeAg having a sequence selected from the group consisting of SEQ. ID. Nos. 1-78.    
     
     
         9 . A method of identifying a binding partner having a sequence that interacts with HBcAg or HBeAg comprising: 
 providing a support comprising HBcAg or HBeAg;    contacting the support with a candidate binding partner having a sequence selected from the group consisting of SEQ. ID. Nos. 1-78; and    detecting a biological complex comprising HBcAg or HBeAg and said candidate binding partner, wherein detection of such complex indicates that said candidate binding partner is a binding partner interacts with HBcAg or HBeAg.    
     
     
         10 . A method of identifying a binding partner that inhibits HBV infection comprising: 
 providing a cell that is infected with HBV;    contacting said cell with a candidate binding partner selected from the group consisting of SEQ. ID. Nos. 1-78; and    determining whether the presence of said candidate binding partner having a sequence is associated with a decrease in HBV infection.    
     
     
         11 . A method of identifying a binding partner that modulates an immune system response comprising: 
 providing a naïve antigen presenting cell;    contacting said naïve antigen presenting cell with a candidate binding partner and a T cell that reacts to HBcAg or HBeAg; and    detecting an inhibition or enhancement of T cell stimulation whereby said binding partner is identified.    
     
     
         12 . The method of  claim 11 , wherein the detection step is performed by evaluating a change in cytokine production or T cell proliferation.  
     
     
         13 . The method of  claim 11 , wherein the candidate binding partner has a sequence selected from the group consisting of SEQ. ID. Nos. 1-78.  
     
     
         14 . A method of determining the presence of HBV in a biological sample comprising: 
 providing a biological sample;    providing a binding partner that binds to HBcAg and/or HBeAg, wherein said binding partner has a sequence selected from the group consisting of SEQ. ID. Nos. 1-78; and    determining whether said binding partner binds to HBcAg and/or HBeAg.    
     
     
         15 . A diagnostic kit for the detection of HBV infection comprising a binding partner, wherein said binding partner has a sequence selected from the group consisting of SEQ. ID. Nos. 1-78.  
     
     
         16 . A method of inhibiting B cell mediated processing and uptake of HBcAg and/or HBeAg comprising: 
 providing a binding partner selected from the group consisting of SEQ. ID. Nos. 1-78; and    determining whether said binding partner inhibits B cell mediated processing and uptake of HBcAg and/or HBeAg.    
     
     
         17 . The method of  claim 16 , wherein the determination of whether said binding partner inhibits B cell mediated processing and uptake of HBcAg and/or HBeAg is accomplished by performing an assay of T cell proliferation or cytokine production.  
     
     
         18 . An isolated or purified peptide consisting essentially of the peptide of SEQ. ID. No. 103 or 104.  
     
     
         19 . A nucleic acid consisting essentially of a nucleic acid sequence encoding the peptide sequence of SEQ. ID. No. 103 or 104.  
     
     
         20 . An isolated or purified biological complex comprising a peptide comprising the sequence of SEQ. ID. No. 74 and a member selected from the group consisting of a peptide consisting essentially of the sequence of SEQ. ID. Nos. 103 or 104, HBcAg, HBeAg, HBV capsid protein, and HBV.