Recombinant vaccines and use thereof

Abstract

The present invention relates to fusion molecules of antigens, the nucleic acids coding therefor and the use of such fusion molecules and nucleic acids. In particular, said invention relates to fusion molecules, comprising an antigen and the trans-membrane region and cytoplasmic region of a MHC molecule and/or the cytoplasmic region of a MHC or a SNARE molecule.

1 . A fusion protein comprising an antigen, and a transmembrane region and a cytoplasmic region of α chain of a MHC molecule or CD1a, CD1b or CD1c but free from (i) α1, α2 and α3 domains of the α chain of a MHC Class I molecule or CD1a, CD1b or CD1c, (ii) β2-microglobulin of a MHC Class I molecule or CD1a, CD1b or CD1c, (iii) α1 and α2 domains of the α chain of a MHC Class II molecule, and (iv) β1 and β2 domains of the β chain of a MHC Class II molecule. 
     
     
         2 . An isolated host cell which comprises the fusion protein as claimed in  claim 1 . 
     
     
         3 . A composition which comprises the fusion protein of  claim 1  in a pharmaceutically acceptable carrier. 
     
     
         4 . The fusion protein of  claim 1 , which includes an amino acid residue sequence selected from the group consisting of SEQ ID NO: 2, 4, 12, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, and 42. 
     
     
         5 . The fusion protein of  claim 1 , which is encoded by a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 11 or SEQ ID NO: 13. 
     
     
         6 . The fusion protein of  claim 1  which includes the amino acid residue sequence of SEQ ID NO: 12. 
     
     
         7 . The fusion protein of  claim 1  which is encoded by a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 11. 
     
     
         8 . The fusion protein of  claim 1  which is encoded by a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 13. 
     
     
         9 . The fusion protein of  claim 1  comprising the amino acid residue sequence of SEQ ID NO: 14. 
     
     
         10 . A composition which comprises the isolated host cell of  claim 2 . 
     
     
         11 . The fusion protein of  claim 1  wherein the antigen is a tumor antigen or a viral antigen. 
     
     
         12 . The fusion protein of  claim 11  wherein the tumor antigen is selected from the group consisting of carcinoembryonic antigen, α1-fetoprotein, isoferritin, fetal sulfoglycoprotein, α2-H-ferroprotein, and γ-fetoprotein and the viral antigen is selected from the group consisting of a viral ribonucleoprotein and a viral envelope protein. 
     
     
         13 . The fusion protein of  claim 1  wherein the transmembrane region and the cytoplasmic region together comprise an amino acid residue sequence selected from the group consisting of SEQ ID NO: 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, and 41. 
     
     
         14 . The fusion protein of  claim 1  wherein the cytoplasmic region comprises an amino acid residue sequence selected from the group consisting of SEQ ID NO:
 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, and 42. 
 
     
     
         15 . The fusion protein of  claim 1  wherein the fusion protein has the amino acid residue sequence of SEQ ID NO: 14. 
     
     
         16 . The fusion protein of  claim 1  wherein the antigen is selected from the group consisting of ART-4, BAGE, ss catenin/m, Bcr-abL CAMEL, CAP-1, CASP-8, CDC27/m, CDK4/m, CEA, claudin-12, c-MYC, CT, Cyp-B, DAM, ELF2M, ETV6-AML1, G250, GAGE, GnT-V, Gap100, HAGE, HER-2/neu, HPV-E7, HPV-E6, HAST-2, hTERT, hTRT, LAGE, LDLR/FUT, MAGE-A, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A5, MAGE-A6, MAGE-A7, MAGE-A8, MAGE-A9, MAGE-A10, MAGE-A11, MAGE-A12, MAGE-B, MAGE-C, MART-1/melan-A, MC1R, myosin/m, MUC1, MUM-1, MUM-2, MUM-3, NA88-A, NF1, NY-ESO-1, NY-BR-1, p190 minor bcr-abL Pml/RARa, PRAME, proteinase-3, PSA, PSM, RAGE, RU1 or RU2, SAGE, SART-1 or SART-3, SCGB3A2, SCP1, SCP2, SCP3, SSX, survivin, TEL/AML1, TPI/m, TRP-1, TRP-2, TRP-2/INT2, TPTE, and WT. 
     
     
         17 . The fusion protein of  claim 1  comprising an amino acid residue sequence selected from the group consisting of SEQ ID NO: 2, 4, 12, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, and 42. 
     
     
         18 . The fusion protein of  claim 1 , wherein the fusion protein additionally comprises a leader sequence. 
     
     
         19 . The fusion protein of  claim 18 , wherein the leader sequence is derived from an MHC molecule. 
     
     
         20 . The fusion protein of  claim 18 , wherein the fusion protein has the following arrangement of segments: N terminus—leader sequence/antigen/transmembrane region/cytoplasmic region—C terminus, and the individual segments optionally are separated from one another by linker sequences. 
     
     
         21 . The fusion protein of  claim 18 , wherein the leader sequence comprises the amino acid sequence of SEQ ID NO: 2.