Ferritin fusion proteins for use in vaccines and other applications
An isolated ferritin fusion protein is provided in which ferritin is fused with a protein or peptide capable of being fused to ferritin without interfering with the polymeric self-assembly of the resulting fusion protein, and the protein may be of the endocapsid form when fused at the C terminus or an exocapsid form when fused at the N terminus. These fusion proteins may self-assemble into a variety of useful higher polymeric forms, e.g., capsid or other polymeric aggregate, and they are advantageous in that they are useful in a variety of applications, including human and veterinary vaccines and therapeutics, blood substitutes, image contrast agents, metal chelating agents, gelling agents, protein purification platforms, and therapeutic receptor-binding proteins.
1. A ferritin fusion protein comprising a fusion protein selected from the group consisting of a ferritin protein fused at the C terminus with a protein or peptide capable of being fused to ferritin without interfering with the polymeric assembly of the resulting fusion protein or a ferritin protein fused at the N terminus with a protein or peptide capable of being fused to ferritin without interfering with the polymeric assembly of the resulting fusion protein wherein the protein fused to ferritin is an antibody.
2. The ferritin fusion protein according to claim 1 wherein the fusion protein forms a polymer aggregate.
3. The ferritin fusion protein according to claim 1 wherein the fusion protein forms a capsid assembly.
4. The ferritin fusion protein according to claim 1 wherein the protein is connected to the ferritin by means of a spacer comprising at least one amino acid.
5. The ferritin fusion protein according to claim 4 wherein the amino acid is glycine.
6. The ferritin fusion protein according to claim 5 wherein the glycine spacer has from one to six glycine units.
7. A ferritin fusion protein comprising a fusion protein selected from the group consisting of a ferritin protein fused at the C terminus with a protein or peptide capable of being fused to ferritin without interfering with the polymeric assembly of the resulting fusion protein or a ferritin protein fused at the N terminus with a protein or peptide capable of being fused to ferritin without interfering with the polymeric assembly of the resulting fusion protein wherein the protein fused to ferritin is selected from the group consisting of hemoglobin, silver condensing peptide, the HIV Tat protein, the small HIV Tat peptide, HIV-1 P24 protein, and viral proteins from the SARS virus.
8. The ferritin fusion protein according to claim 7 wherein the protein fused to ferritin is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:6 and SEQ ID NO: 7.
9. The ferritin fusion protein according to claim 1 wherein the ferritin is selected from the group consisting of the ferritin L chain and the ferritin H chain.
10. The ferritin fusion protein according to claim 1 wherein the ferritin is predominantly comprised of the ferritin L chain.
11. The ferritin fusion protein according to claim 1 wherein the ferritin is predominantly comprised of the ferritin H chain.
12. An immunogenic composition comprising an immunogenic amount of the fusion protein according to claim 7 .
13. A pharmaceutical composition comprising the fusion protein according to claim 1 and a pharmaceutically acceptable vehicle, carrier or excipient.
14. The composition according to claim 13 which is suitable for parenteral, oral, intranasal, subcutaneous, aerosolized or intravenous administration in a human or animal.
15. A method of preparing an immunogenic composition comprising fusing to ferritin at least one immunogenic viral protein or peptide capable of being fused to ferritin without interfering with the polymeric assembly of the resulting fusion protein.
16. A method of eliciting an immunogenic reaction in a human or animal comprising administering to said human or animal an immunologically effective amount of an isolated fusion protein according to claim 7 .
17. An isolated nucleic acid sequence coding for the fusion protein according to claim 1 .
18. A ferritin fusion protein comprising a fusion protein having at least one protein or peptide fused to ferritin at the C terminus, and at least one protein or peptide fused to ferritin at the N terminus wherein said proteins or peptides can be fused to ferritin without interfering with the polymeric assembly of the resulting fusion protein.
19. A ferritin fusion protein according to claim 1 that is prepared using recombinant means.
20. A ferritin fusion protein according to claim 18 that is prepared using recombinant means.
21. A ferritin fusion protein according to claim 1 that is prepared using chemical means.
22. A ferritin fusion protein according to claim 18 that is prepared using chemical means.
23. A ferritin fusion protein comprising a fusion protein selected from the group consisting of a ferritin protein fused at the C terminus with a protein or peptide capable of being fused to ferritin without interfering with the polymeric assembly of the resulting fusion protein or a ferritin protein fused at the N terminus with a protein or peptide capable of being fused to ferritin without interfering with the polymeric assembly of the resulting fusion protein wherein the peptide fused to ferritin is a metal scavenging peptide.
24. A method of metal scavenging comprising introducing the fusion protein of claim 23 into a fluid containing the metals to be scavenged for a time sufficient to allow the metal to bond with the metal scavenging peptide of the fusion protein, and then recovering the fusion protein having the metal bound thereto.
25. A pharmaceutical composition comprising the fusion protein according to claim 7 and a pharmaceutically acceptable vehicle, carrier or excipient.
26. The composition according to claim 25 which is suitable for parenteral, oral, intranasal, subcutaneous, aerosolized or intravenous administration in a human or animal.
27. An isolated nucleic acid sequence coding for the fusion protein according to claim 7 .
28. A pharmaceutical composition comprising the fusion protein according to claim 18 and a pharmaceutically acceptable vehicle, carrier or excipient.
29. The composition according to claim 28 which is suitable for parenteral, oral, intranasal, subcutaneous, aerosolized or intravenous administration in a human or animal.
30. An isolated nucleic acid sequence coding for the fusion protein according to claim 18 .
31. A pharmaceutical composition comprising the fusion protein according to claim 23 and a pharmaceutically acceptable vehicle, carrier or excipient.
32. The composition according to claim 31 which is suitable for parenteral, oral, intranasal, subcutaneous, aerosolized or intravenous administration in a human or animal.
33. An isolated nucleic acid sequence coding for the fusion protein according to claim 23 .
34. A ferritin fusion protein comprising a fusion protein selected from the group consisting of a ferritin protein fused at the C terminus with a protein or peptide capable of being fused to ferritin without interfering with the polymeric assembly of the resulting fusion protein and a ferritin protein fused at the N terminus with a protein or peptide capable of being fused to ferritin without interfering with the polymeric assembly of the resulting fusion protein wherein the protein or peptide fused to ferritin is an immunogenic viral protein or peptide capable of being fused to ferritin without interfering with the polymeric assembly of the resulting fusion protein.
35. A pharmaceutical composition comprising the fusion protein according to claim 34 and a pharmaceutically acceptable vehicle, carrier or excipient.
36. The composition according to claim 35 which is suitable for parenteral, oral, intranasal, subcutaneous, aerosolized or intravenous administration in a human or animal.
37. An isolated nucleic acid sequence coding for the fusion protein according to claim 34 .