HPV Vaccine Comprising Peptides From Host Cell Proteins

Abstract

The present invention relates to a human papillomavirus (HPV) vaccine that comprises peptides from host cell proteins and more particularly, a vaccine that is directed against cancers that are associated with HPV infections, such as cervical cancer, head and neck cancer and skin cancers. The peptides comprise fragments of host cell proteins that have been targeted for degradation by HPV proteins, such as E6 and E7 and are presented on the surface of HPV infected cells in relatively large amounts. These peptides can be recognised by CTL and elicit an immune response, and are therefore ideal tumour-specific markers. The invention also relates to novel peptide: peptide complexes such as peptide/HLA complexes and their use in a tumour-specific vaccine.

1 . A vaccine for treating HPV-associated diseases, comprising: at least one isolated, purified, synthesised or recombinant peptide, wherein the peptide is a fragment of a host cell protein that has been degraded by a human papillomavirus (HPV) oncoprotein, and can elicit a cytotoxic T-lymphocyte (CTL) response when administered to a mammal. 
     
     
         2 . A vaccine according to  claim 1 , wherein the mammal is human. 
     
     
         3 . A vaccine according to  claim 1 , wherein the oncoprotein is E6 or E7. 
     
     
         4 . A vaccine according to  claim 1 , wherein the host cell protein comprises one or more of the proteins shown in Table 3. 
     
     
         5 . A vaccine according to  claim 1 , wherein the peptide is HPV-specific or tumour-specific, meaning that it is presented in high amounts on the cell surface of HPV transformed or tumour cells, relative to normal cells. 
     
     
         6 . A vaccine according to  claim 5 , wherein the peptide is 9-30 amino acids in length. 
     
     
         7 . A vaccine according to  claim 6 , wherein the peptide is 9-11 amino acids in length. 
     
     
         8 . A vaccine according to  claim 7 , wherein said vaccine comprises one or more of the peptides selected from the peptides shown in Table 4 (SEQ ID NO. 1-161). 
     
     
         9 . A vaccine according to  claim 1 , wherein the CTL response is HPV-specific or tumour-specific, meaning that the CTL can recognise HPV-transformed cells or tumour cells expressing the peptide of said vaccine. 
     
     
         10 . A vaccine according to  claims 1 ,  3 ,  4 ,  5 ,  8 , or  9 , which further comprises a major histocompatibility complex molecule. 
     
     
         11 . A vaccine according to  claim 10 , wherein the major histocompatibility complex molecule is a class I molecule. 
     
     
         12 . A vaccine according to  claim 10 , wherein the major histo-compatibility complex molecule is a human leucocyte antigen (HLA). 
     
     
         13 . A vaccine according to  claim 10 , wherein the major histocompatibility complex molecule comprises one or more of those shown in Table 1. 
     
     
         14 . A vaccine for treating HPV-associated diseases, comprising. at least one isolated, purified, synthesised or recombinant nucleic acid molecule encoding at least one peptide selected from the peptides shown in Table 4 (SEQ ID NO. 1-161), and optionally a major histocompatibility complex molecule comprising at least one of the major histocompatibility complex molecules shown in Table 1. 
     
     
         15 . A vaccine according to  claim 14 , wherein the nucleic acid molecule is in a vector and comprises a recombinant construct. 
     
     
         16 . A vaccine according to  claim 15 , wherein the construct is adapted for the expression of said peptide or peptide/HLA complex in a selected host system. 
     
     
         17 . A vaccine according to  claim 14 , wherein the disease is any one of a cervical cancer, a head and neck squamous cell cancer, a non-melanoma skin cancer, a liver cancer, a mesothioloma, or a prostate cancer. 
     
     
         18 . A vector comprising a nucleic acid molecule encoding a peptide selected from the peptides shown in Table 4 (SEQ ID NO. 1-161), and optionally, at least one major histocompatibility complex molecule selected from those listed in Table 1. 
     
     
         19 . A host cell transformed or transfected by a vector according to  claim 18 . 
     
     
         20 . A vector according to  claim 18 , wherein said vector is a cell, plasmid, virus, live organism or other vehicle having incorporated expressibly therein a nucleic acid molecule encoding a peptide selected from the peptides shown in Table 4 (SEQ ID NO. 1-161) and optionally, a major histocompatibility complex molecule selected from those listed in Table 1. 
     
     
         21 . A method of manufacturing a vaccine, which method comprises: culturing a host cell transformed or transfected with a vector according to  claim 18 , and isolating/purifying the resulting construct product. 
     
     
         22 . A method of identifying HPV-specific or tumour-specific CTL, or the CTL receptors thereof, comprising:
 (a) culturing a sample containing CTL with at least one peptide that represents a fragment of a host cell protein that is degraded by HPV proteins when said host cell is transformed or transfected by HPV, whereby said peptide is ultimately presented on a surface of a virally-infected cell; and   (b) selecting CTL that recognise said peptide by binding thereto and, where the CTL receptor is to be identified, determining the nature of the receptor that binds said peptide.   
     
     
         23 . A method according to  claim 22 , wherein the peptide is selected from the peptides shown in Table 4 (SEQ ID NO. 1-161). 
     
     
         24 . A method according to  claim 22  or  claim 23 , wherein the CTL are CD8 +  cells. 
     
     
         25 . A peptide, or nucleic acid molecule encoding same, selected from the peptides shown in Table 4 (SEQ ID NO 1-161). 
     
     
         26 . A method of treatment, comprising administering a vaccine according to  claim 1  to a mammal to be treated. 
     
     
         27 . The method according to  claim 26 , wherein the mammal is human.