Presentation of bioactive proteins
The invention provides a fusion protein comprising an antigen binding domain linked to a bacteriophage decoration (Dec) protein along with a polynucleotide comprising the nucleic acid sequence of the fusion protein and a vector comprising the polynucleotide. Additionally, the invention provides a composition comprising the fusion protein and a virus-like particle (VLP), and a method of treating a disease in a mammal comprising administering a therapeutically effective amount of the composition to the mammal. The invention also provides a method of vaccinating against a disease comprising administering a composition comprising the fusion protein and a VLP encapsulating a protein.
1. A fusion protein comprising an antigen binding domain of a trimerizable tumor necrosis factor super family (TNFSF) protein, and the fusion protein further comprising a trimerizable double stranded DNA bacteriophage decoration (Dec) accessory coat protein.
2. The fusion protein of claim 1 , wherein the antigen binding domain and the Dec protein are joined via a linker region.
3. The fusion protein of claim 2 , IA/herein the linker region comprises 1-100 amino acids.
4. The fusion protein of claim 3 , wherein the linker region comprises glycine and serine residues.
5. The fusion protein of claim 1 , further comprising a tag.
6. The fusion protein of claim 5 , wherein the tag is a polyhistidine tag.
7. The fusion protein of claim 1 , wherein the C-terminus of the Dec protein is linked to the N-terminus of the antigen binding domain.
8. The fusion protein of claim 1 , wherein the Dec protein is a bacteriophage L Dec protein.
9. A polynucleotide encoding the fusion protein of claim 1 .
10. A recombinant vector comprising the polynucleotide of claim 9 .
11. The vector of claim 10 , further comprising a promoter region operably linked to the polynucleotide.
12. A composition comprising the fusion protein of claim 1 and a virus like particle (VLP).
13. The composition of claim 12 , wherein the VLP is a bacteriophage VLP.
14. The composition of claim 13 , wherein the bacteriophage VLP is a bacteriophage P22, VLP.
15. The composition of claim 12 , wherein the VLP encapsulates a guest protein.
16. The, fusion protein of claim 1 , wherein the TNSF protein is a mammalian TNSF protein.
17. The fusion protein of claim 16 , wherein the double stranded DNA bacteriophage decoration (Dec) accessory coat protein can bind to a virus like particle (VLP).
18. A fusion protein comprising an antigen binding domain of a trimerizable tumor necrosis factor super family (TNFSF) protein, the fusion protein further comprising a trimerizable double stranded DNA bacteriophage decoration (Dec) accessory coat protein, and wherein the TNFSF protein is selected from the group consisting of: TNF-α, VEGI, 4-1BBL (TNFSF9), CD 27L (CD70), GIRTL, TRAIL, APRIL, BAFF, FASL, EDA, TWEAK, Lymphotoxin beta, Lymphotoxin alpha, LIGHT, CD30L, RANKL, OX40L, and CD40L.
19. The fusion protein of claim 18 , wherein the TNFSF protein is selected from the group consisting of: CD40L, TRAIL, CD70, 1BBL, MITRE, and TRAIL-T.
20. A fusion protein comprising an antigen binding domain of a trimerizable tumor necrosis factor super family (TNFSF) protein, and the fusion protein further comprising a trimerizable double stranded DNA bacteriophage decoration (Dec) accessory coat protein, wherein the TNFSF protein is CD40L.
21. The fusion protein of claim 20 , wherein the CD40L is murine CD40L, (mCD40L) or human CD40L, (hCD40L).