Mutated parvovirus structural proteins as vaccines

Abstract

The present invention is related to a method for identifying a parvovirus mutated structural protein capable of specifically binding to a binder for an antigen, a parvovirus mutated structural protein which comprises at least one B-cell epitope heterologous to the parvovirus, a multimerc structure comprising the protein, a nucleic acid encoding the protein, a virus or cell comprising the protein, a method of preparing the protein, a medicament comprising the protein, nucleic acid or multimeric structure and its use.

1 - 67 . (canceled) 
     
     
         68 . A method for preventing or treating a disease in a patient in need thereof, the method comprising administering to the patient a medicament comprising at least one parvovirus mutated structural protein, the parvovirus mutated structural protein comprising at least one B-cell epitope heterologous to the parvovirus, wherein the B-cell epitope is located on the surface of the parvovirus mutated structural protein, and wherein the parvovirus mutated structural protein is not used as a vector in gene therapy. 
     
     
         69 . The method of  claim 68 , wherein the B-cell epitope is not identical to a B-cell epitope of a pathogen. 
     
     
         70 . The method of  claim 68 , wherein the parvovirus mutated structural protein comprises at least one B-cell epitope heterologous to the parvovirus which is not identical to a mammalian or pathogen B-cell epitope, but is a functional derivative of a mammalian or pathogen B-cell epitope. 
     
     
         71 . The method of  claim 68 , wherein the B-cell epitope is a tolerogen-derived epitope. 
     
     
         72 . The method of  claim 68 , wherein the B-cell epitope is part of a protein selected from the group consisting of a tumor antigen, a misfolded protein, a serum protein, a membrane protein, a TNF-family member, and an interleukin (IL). 
     
     
         73 . The method of  claim 72 , wherein the B-cell epitope is part of a protein selected from the group consisting of CETP, CD20, acetylcholine receptors, IL13R, EGFR, IgE, Melan A, HMW MAA, CA125, Her2/NEU, L1 cell adhesion molecule, VEGF, EGFR, CD20, TNF-α, IL-6, IL-9, IL-13, IL-17, and β-amyloid. 
     
     
         74 . The method of  claim 72 , wherein the B-cell epitope is a part of human β-amyloid or a human β-amyloid mimotope. 
     
     
         75 . The method of  claim 72 , wherein the B-cell epitope is a part of human IgE or a human IgE mimotope. 
     
     
         76 . The method of  claim 72 , wherein the B-cell epitope is a part of human CETP or a human CETP mimotope. 
     
     
         77 . The method of  claim 72 , wherein the B-cell epitope is a part of human TNF-α or a human TNF-α mimotope. 
     
     
         78 . The method of  claim 72 , wherein the B-cell epitope is a part of human IL-6 or a human IL-6 mimotope. 
     
     
         79 . The method of  claim 72 , wherein the B-cell epitope is a part of human IL-17 or a human IL-17 mimotope. 
     
     
         80 . The method of  claim 72 , wherein the B-cell epitope is a part of human HER2/NEU or a human HER2/NEU mimotope. 
     
     
         81 . The method of  claim 80 , wherein the B-cell epitope comprises or has the sequence QMWAPQWGPD (SEQ ID NO: 225), or a para- or mimotope thereof. 
     
     
         82 . The method of  claim 68 , wherein the B-cell epitope is inserted into I-453 and/or I-587 of the parvovirus mutated structural protein. 
     
     
         83 . The method of  claim 82 , wherein the B-cell epitope is inserted into I-453 and/or I-587 of AAV-1, AAV-2, or AAV-6. 
     
     
         84 . The method of  claim 68 , wherein the medicament is a vaccine. 
     
     
         85 . The method of  claim 68 , wherein the disease is an autoimmune disease, a tumor disease, an allergic disease, a metabolic disease, an inflammatory disease, a neurological disease, or an ophthalmologic disease. 
     
     
         86 . The method of  claim 68 , wherein the medicament breaks immune tolerance. 
     
     
         87 . The method of  claim 68 , wherein the disease is not an infectious disease. 
     
     
         88 . The method of  claim 68 , wherein:
 (a) the disease is an allergic disease and/or asthma, and the B-cell epitope comprises an anti-idiotypic epitope or mimotope of an anti-IgE antibody, and/or an IgE epitope or mimotope;   (b) the disease is Alzheimer's disease, and the B-cell epitope comprises a β-amyloid epitope or mimotope;   (c) the disease is atherosclerosis, and the B-cell epitope comprises a CETP epitope or mimotope;   (d) the disease is a tumor disease, and the B-cell epitope comprises a growth factor receptor or growth factor epitope or mimotope;   (e) the disease is an autoimmune disease and/or a chronic inflammatory disease, preferably rheumatoid arthritis and/or Crohn's disease, and the B-cell epitope comprises an epitope or mimotope of a cytokine; or   (f) the disease is an infectious disease, preferably HIV infection, and the B-cell epitope comprises an epitope or mimotope of a viral receptor.   
     
     
         89 . The method of  claim 88 , wherein:
 (a) the anti-idiotypic epitope or mimotope of an anti-IgE antibody, and/or the IgE epitope or mimotope comprises:
 (i) the sequence of EFCINHRGYWVCGD (SEQ ID NO:84) or INHRGYWV (SEQ ID NO: 203); or 
 (ii) an epitope selected from the group consisting of EKQRNGTLT (SEQ ID NO: 204), EDGQVMDVDLS (SEQ ID NO: 205), TYQCRVTHPHLPRALMR (SEQ ID NO: 206), RHSTTQPRKTKGSG (SEQ ID NO: 207), DSNPRGVSAYLSR (SEQ ID NO: 208), TITCLWDLAPSK (SEQ ID NO: 209), KTKGSGFFVF (SEQ ID NO: 210), THPHLPRALMRS (SEQ ID NO: 211), GETYQCRVTHPHLPRALMRSTTK (SEQ ID NO: 212), LPRALMRS (SEQ ID NO: 213), and a functionally active variant thereof; 
   (b) the β-amyloid epitope or mimotope comprises or has the sequence of DAEFRHDSG (SEQ ID NO: 158) or a functionally active variant thereof;   (c) the CETP epitope or mimotope is selected from the group consisting of PKTVSNLTESSSESVQS (SEQ ID NO: 214), SLMGDEFKAVLET (SEQ ID NO: 215), QHSVAYTFEED (SEQ ID NO: 216), INPEIITRDG (SEQ ID NO: 217), DISLTGDPVITASYL (SEQ ID NO: 218), DISLTGDPVITA (SEQ ID NO: 219), DOSIDFEIDSA (SEQ ID NO: 220), KNVSEDLPLPTFSPTLLGDS (SEQ ID NO: 221), KNVSEDLPLPT (SEQ ID NO: 222), CDSGRVRTDAPD (SEQ ID NO: 223), FPEHLLVDFLQSLS (SEQ ID NO: 224), and a functionally active variant thereof;   (d) the growth factor receptor epitope or mimotope is a HER2/NEU epitope or mimotope;   (e) the cytokine is TNF-α, IL-6, or IL-17; or   (f) the viral receptor is CCR5.   
     
     
         90 . The method of  claim 89 , wherein:
 (i) the HER2/NEU epitope or mimotope comprises the sequence QMWAPQWGPD (SEQ ID NO: 225) or a functionally active variant thereof;   (ii) the cytokine epitope is selected from the group consisting of SSRTPSDKPVAHWANPQAE (SEQ ID NO: 226), SRTPSDKPVAHWANP (SEQ ID NO: 227), SSRTPSDKP (SEQ ID NO: 228), NADGNVDYHMNSVP (SEQ ID NO: 229), DGNVDYHMNSV (SEQ ID NO: 230), RSFKEFLQSSLRALRQ (SEQ ID NO: 231), FKEFLQSSLRA (SEQ ID NO: 232), and a functionally active variant thereof; or   (iii) the epitope of CCR5 is selected from the group consisting of HYAAAQWDFGNTMCQL (SEQ ID NO: 357), YAAQWDFGNTMCQ (SEQ ID NO: 358), RSQKEGLHYT (SEQ ID NO: 359), and a functionally active variant thereof.