Homodimeric protein constructs
The present disclosure relates to recombinant fusion proteins, such as human antibody-based molecules called Vaccibodies, which are able to trigger both a T cell- and B cell immune response. The present disclosure also relates to a method of treating a cancer or an infectious disease by means of these specific fusion proteins.
1. A nucleic acid molecule encoding a monomeric protein which can form a homodimeric protein of two identical amino acid chains, said homodimeric protein being useful as a vaccine, each amino acid chain comprising a targeting unit comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in positions 5-70 of SEQ ID NO: 1, and an antigenic unit, the targeting unit and the antigenic unit being connected through a dimerization motif,
wherein said homodimeric protein provides MHC class I cross-presentation to CD8+ T cells, and is capable of eliciting an immune response against said antigenic unit.
2. A homodimeric protein of two identical amino acid chains, each amino acid chain encoded by the nucleic acid molecule according to claim 1 for use as a vaccine.
3. A pharmaceutical composition comprising a homodimeric protein of two identical amino acid chains, each amino acid chain encoded by the nucleic acid molecule according to claim 1 , said homodimeric protein being useful as a vaccine.
4. A host cell comprising the nucleic acid molecule according to claim 1 .
5. A method for preparing a homodimeric protein, the method comprising:
a) transfecting the nucleic acid molecule according to claim 1 into a cell population;
b) culturing the cell population; and
c) collecting and purifying the homodimeric protein expressed from the cell population
wherein said purified homodimeric protein comprises two identical amino acid chains, each amino acid chain comprising a targeting unit comprising an amino acid sequence having at least 98% sequence identity to the amino acid sequence set forth in positions 5-70 of SEQ ID NO: 1, and an antigenic unit comprising a HPV antigen, the targeting unit and the antigenic unit being connected through a dimerization motif,
wherein said homodimeric protein provides MHC class I restricted cross presentation to CD8+ T cells, and is capable of eliciting an immune response against said antigenic unit,
wherein said homodimeric protein is useful as a vaccine.
6. A vaccine against a cancer or an infectious disease comprising an immunologically effective amount of a homodimeric protein of two identical amino acid chains, each amino acid chain encoded by the
nucleic acid molecule according to claim 1 , wherein said vaccine is able to trigger a T-cell-immune response and wherein said homodimeric protein contain an antigenic unit comprising a HPV antigen.
7. The vaccine according to claim 6 , wherein said cancer is a HPV induced cancers.
8. The vaccine according to claim 6 , wherein said infectious disease is HPV.
9. The nucleic acid molecule of claim 1 , wherein said nucleic acid molecule comprises a vector.
10. The nucleic acid molecule of claim 1 , wherein the antigen is selected from the list consisting of: HPV antigens E1, E2, E4, E6 and E7.
11. The vaccine of claim 6 , wherein the HPV antigen is selected from the list consisting of: E1, E2, E4, E6 and E7.
12. The nucleic acid molecule of claim 1 , wherein said antigenic unit comprises a cancer associated or a cancer specific antigen.
13. The nucleic acid molecule of claim 12 , wherein said cancer associated or cancer specific antigen comprises a melanoma antigen, a prostate cancer antigen, an HPV antigen, or cervix cancer antigen.