Antibodies For Oncogenic Strains Of HPV And Methods Of Their Use

Abstract

The subject invention provides antibodies, including polyclonal and monoclonal antibodies, that bind to E6 proteins from at least three oncogenic strains of HPV. In general, the antibodies bind to amino acids motifs that are conserved between the E6 proteins of different HPV strains, particularly HPV strains 16 and 18. The subject antibodies may be used to detect HPV E6 protein in a sample, and, accordingly, the antibodies find use in a variety of diagnostic applications, including methods of diagnosing cancer. Kits for performing the subject methods and containing the subject antibodies are also provided.

1 . A monoclonal antibody that specifically binds to a sub-sequence of a common sequence of at least two E6 proteins of HPV strains 16, 18, and 45, wherein the common sequence is an amino acid sequence motif that is generally conserved between the at least two E6 proteins. 
     
     
         2 . The monoclonal antibody of  claim 1 , wherein the antibody specifically binds to an E6 peptide having SEQ ID NO: 7, 8, or 60. 
     
     
         3 . The monoclonal antibody of  claim 1 , wherein the antibody specifically binds to an E6 peptide having SEQ ID NO: 9, 10, or 61. 
     
     
         4 . The monoclonal antibody of  claim 1 , wherein the antibody specifically binds to an E6 peptide having SEQ ID NO: 11, 12, or 62. 
     
     
         5 . The monoclonal antibody of  claim 1 , wherein the antibody specifically binds to an HPV E6 peptide having SEQ ID NO: 1, 2, 3, 4, 5, 6, 57, 58, or 59. 
     
     
         6 . The monoclonal antibody of  claim 1 , wherein the antibody is cross-reactive with at least three human papilloma virus E6 proteins. 
     
     
         7 . The monoclonal antibody of  claim 1 , wherein the antibody is cross-reactive with at least four human papilloma virus E6 proteins. 
     
     
         8 . The monoclonal antibody of  claim 1 , wherein the antibody has a binding affinity of less than 10 −7  M. 
     
     
         9 . The monoclonal antibody of  claim 1 , wherein the antibody has a binding affinity of less than 10 −8  M. 
     
     
         10 . The monoclonal antibody of  claim 1 , wherein the antibody has a binding affinity of less than 10 −9  M. 
     
     
         11 . An antibody composition comprising a mixture of monoclonal antibodies that specifically bind to E6 proteins of HPV strains 16, 18, 31, 33 and 45, wherein at least one of said monoclonal antibodies is cross-reactive with at least two HPV E6 proteins, wherein the antibody specifically binds to an E6 peptide comprising a sub-sequence of a common sequence of at least two E6 proteins of HPV strains 16, 18, and 45, wherein the common sequence is an amino acid sequence motif that is generally conserved between the at least two E6 proteins. 
     
     
         12 . The antibody composition of  claim 11 , wherein at least one of said monoclonal antibodies specifically binds to an E6 peptide having SEQ ID NO: 1, 2, 3, 4, 5, 6, 57, 58, or 59. 
     
     
         13 . The antibody composition of  claim 11 , wherein said mixture of monoclonal antibodies specifically bind to E6 proteins of HPV strains 16, 18, 31, 33, 45, 52 and 58. 
     
     
         14 . The antibody composition of  claim 11 , wherein said mixture of monoclonal antibodies specifically bind to E6 proteins of HPV strains 16, 18, 31, 33, 45, 52, 58, 35 and 59. 
     
     
         15 . A diagnostic kit for the detection of an HPV E6 polypeptide in a sample, comprising: the antibody composition of  claim 11 . 
     
     
         16 . The diagnostic kit of  claim 15 , wherein said monoclonal antibodies are labeled. 
     
     
         17 . The diagnostic kit of  claim 15 , further comprising a PDZ domain polypeptide that binds to an oncogenic HPV E6 polypeptide in a sample. 
     
     
         18 . A method of detecting an HPV E6 protein in a sample, comprising:
 contacting an antibody composition of  claim 11  with said sample; and   detecting any binding of said antibody to said sample;   wherein binding of said antibody to said sample indicates the presence of an HPV E6 protein.   
     
     
         19 . The method of  claim 18 , wherein said sample is suspected of containing an oncogenic strain of HPV. 
     
     
         20 . A method of detecting the presence of an oncogenic HPV E6 protein in a sample, said method comprising:
 contacting a sample with a PDZ domain polypeptide; and   detecting any binding of said oncogenic HPV E6 protein in said sample to said PDZ domain polypeptide using an antibody composition of  claim 11 ;   wherein binding of said oncogenic HPV E6 protein to said PDZ domain polypeptide indicates the presence of an oncogenic HPV E6 protein in said sample.   
     
     
         21 . A system for detecting the presence of an oncogenic HPV E6 polypeptide in a sample, said system comprising:
 a first and a second binding partner for an oncogenic HPV E6 polypeptide, wherein said first binding partner is a PDZ domain protein and said second binding partner is an antibody of  claim 1 .   
     
     
         22 . The system of  claim 21 , wherein at least one of said binding partners is attached to a solid support.