Recombinant vaccines and use thereof
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 nucleic acid molecule which codes for a fusion protein comprising an antigen, and a transmembrane region and a cytoplasmic region of a chain of an human leukocyte antigen (HLA) molecule but is free from (i) α1, α2 and α3 domains of the α chain of an HLA Class I molecule, (ii) β2-microglobulin of an HLA Class I molecule, (iii) α1, α2 domains of the α chain of an HLA Class II molecule, and (iv) β1 and β2 domains of the β chain of an HLA Class II molecule.
2. The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule is RNA.
3. The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule is mRNA.
4. The nucleic acid molecule of claim 1 , wherein the HLA molecule is an HLA class I molecule.
5. The nucleic acid molecule of claim 1 , wherein the HLA molecule is an HLA class I molecule selected from the group consisting of: HLA-A, HLA-B, HLA-C, HLA-E, and HLA-F.
6. The nucleic acid molecule of claim 1 , wherein the HLA molecule is an HLA class II molecule.
7. The nucleic acid molecule of claim 1 , wherein the HLA molecule is an HLA class II molecule selected from the group consisting of: HLA-DQα, HLA-DQβ, HLA-DPα, HLA-DPβ, HLA-DRα, and HLA-DRβ.
8. The nucleic acid molecule of claim 1 , further comprising a leader sequence.
9. The nucleic acid molecule of claim 8 , wherein the leader sequence is a secretion signal.
10. The nucleic acid molecule of claim 8 , wherein the leader sequence is derived from an HLA molecule.
11. The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule has the followng arrangment of segments: N-terminus-leader sequence/antigen/transmembrane region/cytoplasmic region-C-terminus and the individual segments are separated from one another by linker sequences.
12. The nucleic acid molecule of claim 1 , where the fusion protein comprises the amino acid residue sequence of SEQ ID NO: 6.
13. The nucleic acid molecule of claim 1 , wherein the antigen is a tumor antigen.
14. An isolated host cell which comprises the nucleic acid molecule of claim 1 .
15. A composition which comprises the isolated host cell of claim 14 .
16. A composition which comprises the nucleic acid molecule of claim 1 in a pharmaceutically acceptable carrier.
17. A method for inducing the formation of MHC/peptide complexes in a cell, the method comprising contacting the cell with at least one nucleic acid molecule of claim 1 .
18. A method for increasing the number of MCH/peptide complexes in a cell, wherein the method comprises providing to the cell one or more nucleic acid molecules of claim 1 .
19. A method for increasing the presentation of cell surface molecules on antigen-presenting cells (APCs), wherein the method comprises providing to the APCs one or more nucleic acid molecules of claim 1 .
20. A method for inducing an immune response in a living creature, wherein the method comprises administering to the living creature one or more nucleic acid molecule of claim 1 or host cells comprising the nucleic acid molecule of claim 1 .
21. A method for stimulating or activating T cells, wherein the method comprises contacting the T cell or administering to a living creature one or more nucleic acid molecule of claim 1 or host cells comprising the nucleic acid molecule of claim 1 .