Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens
View Patent ↗Disclosed herein are methods and compositions for enhancing the immunogenicity of a preselected protein or peptide antigen in a mammal. Immunogenicity is enhanced by fusing the preselected antigen to an immunoglobulin heavy chain constant region to produce an Fc-antigen fusion protein. The Fc-antigen fusion proteins bind Fc receptors on the surface of antigen presenting cells, thereby targeting the antigen to the antigen presenting cells in the mammal. In addition, disclosed is a family of adjuvants, for example, an Fc-adjuvant fusion protein, for use in combination with the Fc-antigen fusion proteins to enhance or modulate a particular immune response against the preselected antigen.
1. A method for eliciting an immune response against an antigen in a mammal, the method comprising:
administering to the mammal intramuscularly, intravenously, transdermally or subcutaneously, a fusion protein comprising an antigen linked by a polypeptide bond to an immunoglobulin heavy chain constant region whose ability to bind an Fc receptor is not modified by mutation, thereby to elicit an immune response against the antigen, wherein the fusion protein lacks an immunoglobulin variable domain and the antigen is selected from the group consisting of Prostate-Specific Membrane Antigen, an ectodomain of a cytokine receptor, a viral protein and a tumor-specific protein, the antigen of the fusion protein eliciting a stronger immune response in the mammal than the antigen alone.
2. The method of claim 1 , further comprising administering the fusion protein in combination with an adjuvant in an amount sufficient to enhance the immune response against the antigen of the fusion protein relative to the immune response against the antigen of the fusion protein administered without the adjuvant.
3. The method of claim 2 , wherein the fusion protein and adjuvant are administered simultaneously.
4. The method of claim 2 , wherein the adjuvant comprises a fusion protein comprising an immunoglobulin heavy chain constant region linked by a polypeptide bond to an adjuvant protein.
5. The method of claim 1 or 4 , wherein the immunoglobulin heavy chain constant region comprises an immunoglobulin hinge region.
6. The method of claim 5 , wherein the immunoglobulin heavy chain constant region comprises an immunoglobulin heavy chain constant region domain selected from the group consisting of a CH2 domain, a CH3 domain, and a CH4 domain.
7. The method of claim 5 , wherein the immunoglobulin heavy chain constant region comprises a CH2 domain and a CH3 domain.
8. The method of claim 1 or 4 , wherein the immunoglobulin heavy chain constant region is an immunoglobulin heavy chain constant region present in the same species as the mammal.
9. The method of claim 8 , wherein the immunoglobulin heavy chain constant region is a human immunoglobulin heavy chain constant region.
10. The method of claim 4 , wherein the adjuvant protein is a cytokine.
11. The method of claim 10 , wherein the cytokine is a cytokine present in the same species as the mammal.
12. The method of claim 11 , wherein the cytokine is a human cytokine.
13. The method of claim 1 , wherein the mammal is a human.
14. A composition for eliciting an immune response against an antigen in a mammal, the composition comprising:
an adjuvant; and
an antigen fusion protein comprising an antigen linked by a polypeptide bond to an immunoglobulin heavy chain constant region whose ability to bind an Fc receptor is not modified by mutation, wherein the antigen fusion protein lacks an immunoglobulin variable domain and the antigen of the fusion protein is capable of eliciting a stronger immune response in the mammal than the antigen alone, wherein the antigen is selected from the group consisting of Prostate-Specific Membrane Antigen, an ectodomain of a cytokine receptor, a viral protein and a tumor-specific protein, the composition being formulated for intramuscular, intravenous, transdermal or subcutaneous administration.
15. The composition of claim 14 , wherein the adjuvant comprises a fusion protein comprising an immunoglobulin constant region linked by a polypeptide bond to an adjuvant protein.
16. The composition of claim 14 or 15 , wherein the immunoglobulin heavy chain constant region comprises an immunoglobulin hinge region.
17. The composition of claim 16 , wherein the immunoglobulin heavy chain constant region comprises an immunoglobulin heavy chain constant region domain selected from the group consisting of a CH2 domain, a CH3 domain, and a CH4 domain.
18. The composition of claim 16 , wherein the immunoglobulin heavy chain constant region comprises a CH2 domain and a CH3 domain.
19. The composition of claim 14 , wherein the adjuvant comprises an oligonucleotide CpG sequence.
20. The composition of claim 14 , wherein the adjuvant comprises a cytokine.
21. The composition of claim 20 , wherein the cytokine is a human cytokine.
22. The composition of claim 14 or 15 , wherein the immunoglobulin heavy chain constant region is a human immunoglobulin heavy chain constant region.
23. The composition of claim 15 , wherein the adjuvant protein is a cytokine.
24. The method of claim 1 , wherein the fusion protein further comprises an adjuvant linked by a polypeptide bond to at least one of the antigen and the immunoglobulin heavy chain constant region.
25. The composition of claim 14 , wherein the adjuvant is linked by a polypeptide bond to at least one of the antigen and the immunoglobulin heavy chain constant region.