Albumin binding peptide conjugates and methods thereof
The present invention provides a conjugate comprising an albumin binding peptide and a cargo, compositions for directing cargos to the lymphatic system, and vaccines. The methods of the invention can be used to increase an immune response, or to treat cancer or an infectious disease.
1. A conjugate for priming an endogenous immune response comprising:
(a) an albumin binding peptide; and
(b) an immunomodulatory molecule, wherein the immunomodulatory molecule is a peptide antigen or an immunostimulatory oligonucleotide,
and wherein the albumin binding peptide is operatively coupled to the immunomodulatory molecule with or without a linker domain, thereby providing a conjugate for priming an endogenous immune response.
2. The conjugate of claim 1 , wherein the albumin binding peptide is covalently linked to the immunomodulatory molecule, or the albumin binding peptide is operatively coupled to the immunomodulatory molecule via a linker domain.
3. The conjugate of claim 2 , wherein the linker domain comprises a Gly-Ser linker or a polyethylene glycol (PEG) linker.
4. The conjugate of claim 3 , wherein the Gly-Ser linker is a (Gly 4 Ser) n (SEQ ID NO: 44) linker, and wherein n is 1-6.
5. The conjugate of claim 3 , wherein the PEG linker is a PEG 2000 linker.
6. The conjugate of claim 1 , wherein the peptide antigen is a cancer antigen or a melanoma antigen.
7. The conjugate of claim 1 , wherein the immunostimulatory oligonucleotide is CpG DNA.
8. The conjugate of claim 1 , wherein the albumin binding peptide comprises the amino acid sequence DICLPRWGCLW (SEQ ID NO: 9).
9. A vaccine comprising the conjugate of claim 1 and a pharmaceutically acceptable carrier or excipient.
10. The vaccine of claim 9 further comprising an adjuvant.
11. A composition for directing immunomodulatory molecules to the lymphatic system, wherein the composition comprises a conjugate comprising:
(a) an albumin binding peptide; and
(b) an immunomodulatory molecule,
wherein the immunomodulatory molecule is a peptide antigen or an immunostimulatory oligonucleotide, and wherein the albumin binding peptide is operatively coupled to the immunomodulatory molecule with or without a linker domain.
12. The composition of claim 11 , wherein the conjugate exhibits increased accumulation in the lymph node when administered to the subject in vivo compared to administration of the antigen alone.
13. An immunogenic composition comprising the conjugate of claim 1 .
14. An immunogenic composition comprising the vaccine of claim 9 .
15. A nucleic acid molecule encoding the conjugate according to claim 1 .
16. A recombinant expression vector comprising a nucleic acid molecule according to claim 15 .
17. A host cell transformed with the recombinant expression vector according to claim 16 .
18. The composition of claim 11 , wherein the albumin binding peptide is covalently linked to the immunomodulatory molecule, or the albumin binding peptide is operatively coupled to the immunomodulatory molecule via a linker domain.
19. The composition of claim 18 , wherein the linker domain comprises a Gly-Ser linker or a polyethylene glycol (PEG) linker.
20. The composition of claim 19 , wherein the Gly-Ser linker is a (Gly 4 Ser) n (SEQ ID NO: 44) linker.
21. The composition of claim 19 , wherein the PEG linker is a PEG 2000 linker.
22. The composition of claim 11 , wherein the peptide antigen is a cancer antigen or a melanoma antigen.
23. The composition of claim 11 , wherein the immunostimulatory oligonucleotide is CpG DNA.
24. The composition of claim 11 , wherein the albumin binding peptide comprises the amino acid sequence DICLPRWGCLW (SEQ ID NO: 9).