US2003152582A1PendingUtilityA1

CTL epitopes from EBV

41
Priority: Jul 10, 1997Filed: Feb 3, 2003Published: Aug 14, 2003
Est. expiryJul 10, 2017(expired)· nominal 20-yr term from priority
Inventors:Scott BurrowsRajiv KhannaMartina Alison Sherritt
A61P 43/00A61P 31/12A61P 35/00A61P 31/20C12N 2710/16222C12N 2710/16622C07K 14/005A61K 40/46A61K 40/11A61K 39/00Y02A50/30
41
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Claims

Abstract

The present invention provides cytotoxic Epstein-Barr virus (EBV) T-cell epitopes derived from EBV structural antigens. Preferred epitopes include YLLEMLWRL (SEQ ID NO: 1), YFLEILWGL (SEQ ID NO: 32), YLLEILWRL (SEQ ID NO: 33), YLQQNWWTL (SEQ ID NO: 6), LLLALLFWL (SEQ ID NO: 2), LLVDLLWLL (SEQ ID NO: 3), LLLIALWNL (SEQ ID NO: 4), WLLLFLAIL (SEQ ID NO: 5), TLLVDLLWL (SEQ ID NO: 7), LLWLLLFLA (SEQ ID NO: 8), ILLIIALYL (SEQ ID NO: 9), VLFIFGCLL (SEQ ID NO: 10), RLGATIWQL (SEQ ID NO: 11), ILYFIAFAL (SEQ ID NO: 15), SLVIVTTFV (SEQ ID NO: 17), LMIIPLINV (SEQ ID NO: 20), TLFIGSHVV (SEQ ID NO: 24), LIPETVPYI (SEQ ID NO: 26), VLQWASLAV (SEQ ID NO: 27) and QLTPHTKAV (SEQ ID NO: 29). The present invention also provides methods of treating or preventing EBV infection in subjects which involve administration of EBV cytotoxic T-cell epitopes.

Claims

exact text as granted — not AI-modified
1 . A cytotoxic Epstein-Barr virus (EBV) T-cell epitope the epitope being derived from an EBV structural antigen.  
     
     
         2 . A cytotoxic EBV T-cell epitope as claimed in  claim 1  wherein the EBV structural antigen is gp85 or gp350.  
     
     
         3 . A cytotoxic T-cell epitope, the epitope being selected from the group consisting of YLLEMLWRL (SEQ ID NO: 1), YFLEILWGL (SEQ ID NO: 32), YLLEILWRL (SEQ ID NO: 33), YLQQNWWTL (SEQ ID NO: 6), LLLALLFWL (SEQ ID NO: 2), LLVDLLWLL (SEQ ID NO: 3), LLLIALWNL (SEQ ID NO: 4), WLLLFLAIL (SEQ ID NO: 5), TLLVDLLWL (SEQ ID NO: 7), LLWLLLFLA (SEQ ID NO: 8), ILLIIALYL (SEQ ID NO: 9), VLFIFGCLL (SEQ ID NO: 10), RLGATIWQL (SEQ ID NO: 11), ILYFIAFAL (SEQ ID NO: 15), SLVIVTTFV (SEQ ID NO: 17), LMIIPLINV (SEQ ID NO: 20), TLFIGSHVV (SEQ ID NO: 24), LIPETVPYI (SEQ ID NO: 26), VLQWASLAV (SEQ ID NO: 27) and QLTPHTKAV (SEQ ID NO: 29).  
     
     
         4 . A subunit vaccine including a cytotoxic Epstein-Barr virus (EBV) T-cell epitope as claimed in  claim 1  or  claim 2 .  
     
     
         5 . A subunit vaccine including at least one T-cell epitope selected from the group consisting of YLLEMLWRL (SEQ ID NO: 1), YFLEILWGL (SEQ ID NO: 32), YLLEILWRL (SEQ ID NO: 33), YLQQNWWTL (SEQ ID NO: 6), LLLALLFWL (SEQ ID NO: 2), LLVDLLWLL (SEQ ID NO: 3), LLLIALWNL (SEQ ID NO: 4), WLLLFLAIL (SEQ ID NO: 5), TLLVDLLWL (SEQ ID NO: 7), LLWLLLFLA (SEQ ID NO: 8), ILLIIALYL (SEQ ID NO: 9), VLFIFGCLL (SEQ ID NO: 10), RLGATIWQL (SEQ ID NO: 11), ILYFIAFAL (SEQ ID NO: 15), SLVIVTTFV (SEQ ID NO: 17), LMIIPLINV (SEQ ID NO: 20), TLFIGSHVV (SEQ ID NO: 24), LIPETVPYI (SEQ ID NO: 26), VLQWASLAV (SEQ ID NO: 27) and QLTPHTKAV (SEQ ID NO: 29).  
     
     
         6 . A subunit vaccine as claimed in  claim 5  wherein the epitope is selected from the group consisting of YLLEMLWRL (SEQ ID NO: 1), YLQQNWWTL (SEQ ID NO: 6), YFLEILWGL (SEQ ID NO: 32), YLLEILWRL (SEQ ID NO: 33), SLVIVTTFV (SEQ ID NO: 17), LMIIPLINV (SEQ ID NO: 20), TLFIGSHVV (SEQ ID NO: 24), and VLQWASLAV(SEQ ID NO: 27).  
     
     
         7 . A subunit vaccine as claimed in any one of  claims 4  to  6  wherein the vaccine further includes at least one antigen to which the individual will mount an anamnestic response in addition to the at least one cytotoxic T-cell epitope.  
     
     
         8 . A subunit vaccine as claimed in  claim 7  wherein the at least one antigen is selected from the group consisting of tetanus toxoid, diphtheria toxoid, Bordetella pertussis antigens, poliovirus antigens, purified protein derivative (PPD), gp350 protein, helper epitopes and combinations thereof.  
     
     
         9 . A subunit vaccine as claimed in  claim 8  wherein the at least one antigen is tetanus toxoid.  
     
     
         10 . A subunit vaccine as claimed in any one of  claims 4  to  9  in which the vaccine includes a water-in-oil formulation.  
     
     
         11 . An isolated nucleic acid sequence encoding a cytotoxic Epstein-Barr virus (EBV) T-cell epitope as claimed in  claim 1  or  claim 2 .  
     
     
         12 . An isolated nucleic acid sequence encoding at least one of the cytotoxic T-cell epitopes selected from the group consisting of YLLEMLWRL (SEQ ID NO: 1), YFLEILWGL (SEQ ID NO: 32), YLLEILWRL (SEQ ID NO: 33), YLQQNWWTL (SEQ ID NO: 6), LLLALLFWL (SEQ ID NO: 2), LLVDLLWLL (SEQ ID NO: 3), LLLIALWNL (SEQ ID NO: 4), WLLLFLAIL (SEQ ID NO: 5), TLLVDLLWL (SEQ ID NO: 7), LLWLLLFLA (SEQ ID NO: 8), ILLIIALYL (SEQ ID NO: 9), VLFIFGCLL (SEQ ID NO: 10), RLGATIWQL (SEQ ID NO: 11), ILYFIAFAL (SEQ ID NO: 15), SLVIVTTFV (SEQ ID NO: 17). LMIIPLINV (SEQ ID NO: 20), TLFIGSHVV (SEQ ID NO: 24), LIPETVPYI (SEQ ID NO: 26), VLQWASLAV (SEQ ID NO: 27) and QLTPHTKAV (SEQ ID NO: 29).  
     
     
         13 . An isolated nucleic acid sequence as claimed in  claim 12  wherein the epitope is selected from the group consisting of YLLEMLWRL (SEQ ID NO: 1), YLQQNWWTL (SEQ ID NO: 6), YFLEILWGL (SEQ ID NO: 32), YLLEILWRL (SEQ ID NO: 33), SLVIVTTFV (SEQ ID NO: 17), LMIIPLINV (SEQ ID NO: 20), TLFIGSHVV (SEQ ID NO: 24), and VLQWASLAV (SEQ ID NO: 27).  
     
     
         14 . A vector including a nucleic acid sequence as claimed in any one of  claims 11  to  13 .  
     
     
         15 . A vector as claimed in  claim 14  in which the vector is a bacteria, preferably Salmonella spp.  
     
     
         16 . A vector as claimed in  claim 14  in which the vector is a virus. preferably Adenovirus. Retrovirus or Vaccinia, and most preferably Modified Vaccinia Ankara.  
     
     
         17 . An isolated polypeptide, the polypeptide including at least one EBV CTL epitope as claimed in any one of  claims 1  to  3 .  
     
     
         18 . A method of preparing a composition for use in inducing CTLs in a subject, the method including admixing at least one epitope as claimed in any one of  claims 1  to  3  with at least one pharmaceutically acceptable carrier, diluent or excipient.  
     
     
         19 . A method of reducing the risk of EBV infection in a subject which method includes administering to the subject an effective amount of: 
 (1) at least one CTL epitope as claimed in any one of  claims 1  to  3 ;    (2) a subunit vaccine as claimed in any one of  claims 4  to  10 ;    (3) a nucleic acid sequence as claimed in any one of  claims 11  to  13 ;    (4) a vector as claimed in any one of  claims 14  to  16 ; or    (5) a polypeptide as claimed in  claim 17 .    
     
     
         20 . A method of treating or preventing nasopharyngeal carcinoma or Hodgkin's disease in a subject which method includes administering to the subject an effective amount of at least one CTL epitope derived from an EBV structural or latent antigen.  
     
     
         21 . A method according to  claim 20  wherein the EBV structural antigen is gp85 or gp350.  
     
     
         22 . A method according to  claim 20  wherein the EBV latent antigen is LMP1 or LMP2.  
     
     
         23 . A method according to  claim 20  wherein at least one CTL epitope selected from the group consisting of YLLEMLWRL (SEQ ID NO: 1), YFLEILWGL (SEQ ID NO: 32), YLLEILWRL (SEQ ID NO: 33), YLQQNWWTL (SEQ ID NO: 6), LLLALLFWL (SEQ ID NO: 2), LLVDLLWLL(SEQ ID NO: 3), LLLIALWNL (SEQ ID NO: 4), WLLLFLAIL (SEQ ID NO: 5), TLLVDLLWL (SEQ ID NO. 7). LLWLLLFLA (SEQ ID NO: 8), ILLIIALYL (SEQ ID NO: 9), VLFIFGCLL (SEQ ID NO: 10), RLGATIWQL (SEQ ID NO: 11), ILYFIAFAL (SEQ ID NO: 15), SLVIVTTFV (SEQ ID NO: 17), LMIIPLINV (SEQ ID NO: 20), TLFIGSHVV (SEQ ID NO: 24), LIPETVPYI (SEQ ID NO: 26), VLQWASIAV (SEQ ID NO: 27) and QLTPHTKAV (SEQ ID NO: 29), is administered to the subject.  
     
     
         24 . A method of treating or preventing growth of NPC cells in a subject in need thereof which method includes administering to the subject at least one CTL epitope derived from an EBV structural or latent antigen.  
     
     
         25 . A method according to  claim 24  wherein the EBV structural antigen is gp85 or gp350.  
     
     
         26 . A method according to  claim 24  wherein the EBV latent antigen is LMP1 or LMP2.  
     
     
         27 . A method according to  claim 27  wherein at least one CTL epitope selected from the group consisting of YLLEMLWRL (SEQ ID NO: 1), YFLEILWGL (SEQ ID NO: 32), YLLEILWRL (SEQ ID NO: 33), YLQQNWWTL (SEQ ID NO: 6), LLLALLFWL (SEQ ID NO: 2), LLVDLLWLL (SEQ ID NO: 3), LLLIALWNL (SEQ ID NO: 4), WLLLFLAIL (SEQ ID NO: 5), TLLVDLLWL (SEQ ID NO: 7), LLWLLLFLA (SEQ ID NO: 8), ILLIIALYL (SEQ ID NO: 9), VLFIFGCLL (SEQ ID NO: 10), RLGATIWQL (SEQ ID NO: 11), ILYFIAFAL (SEQ ID NO: 15), SLVIVTTFV (SEQ ID NO: 17), LMIIPLINV (SEQ ID NO: 20), TLFIGSHVV (SEQ ID NO: 24), LIPETVPYI (SEQ ID NO: 26), VLQWASLAV (SEQ ID NO: 27) and QLTPHTKAV (SEQ ID NO: 29), is administered to the subject.  
     
     
         28 . A method of treating or preventing the growth of NPC or HD cells in a first subject which method includes transferring to the first subject EBV-specific CTLs which recognise NPC or HD cells.  
     
     
         29 . A method as claimed in  claim 28  wherein the EBV-specific CTLs are obtained from the first subject by in vitro stimulation of CTLs by exposure to EBV CTL epitopes.  
     
     
         30 . A method as claimed in  claim 28  wherein the EBV-specific CTLs are obtained from a second subject, wherein the second subject is infected with EBV but does not have NPC or HD.  
     
     
         31 . A method as claimed in  claim 26  wherein the EBV-specific CTLs are LMP1 and/or LMP2-specific CTLs.  
     
     
         32 . A method of reducing the risk of infectious mononucleosis or post transplantation lymphoproliferative disease in a subject which method includes administering to the subject an effective amount of: 
 (1) at least one CTL epitope as claimed in any one of  claims 1  to  3 ;    (2) a subunit vaccine as claimed in any one of  claims 4  to  10 ;    (3) a nucleic acid sequence as claimed in any one of  claims 11  to  13 ;    (4) a vector as claimed in any one of  claims 14  to  16 ; or    (5) a polypeptide as claimed in  claim 17.

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