High Molecular Weight Amyloid Beta As a Carrier for the Oral Delivery of Vaccine Antigens

• US 20100297160A1
• Filed: 05/14/2010
• Published: 11/25/2010
• Est. Priority Date: 05/14/2009
• Status: Abandoned Application

• Current Assignee: Medical College of Georgia (University System of Georgia)
• Original Assignee: Medical College of Georgia (University System of Georgia)
• Inventors: Bartlett, Michael, Mruthinti, Shyamala
• Application Number:
  US12/780,628
• Publication Number:
  US 20100297160A1
• Time in Patent Office: Days
• US Class Current: 424/185.1
• CPC Class Codes: A61K 2039/542 oral/gastrointestinal
• CPC Class Codes: A61K 2039/622 non-covalent binding
• CPC Class Codes: A61K 39/0007 Nervous system antigens; Prions
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

Compositions and methods are provided for stabilizing polypeptide antigens such as amyloid-beta (Aβ) to produce vaccines for oral delivery. One embodiment provides an immunogenic polypeptide complex of Aβ₄₂ and an fragment of receptor for advanced glycation endproducts (RAGE).

Claims

1. A pharmaceutical composition comprising an effective amount of an immunogenic polypeptide complex in a pharmaceutically acceptable excipient, wherein the immunogenic polypeptide complex comprises an amyloid beta 42 (Aβ

₄₂) polypeptide and an immunogenic fragment of receptor for advanced glycation endproducts (RAGE), wherein the immunogenic fragment of RAGE can bind Aβ

₄₂.

2. The pharmaceutical composition of claim 1, wherein the Aβ

₄₂ polypeptide and the immunogenic fragment of RAGE are in approximately equimolar amounts.

3. The pharmaceutical composition of claim 1, wherein the immunogenic fragment of RAGE comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:

5.

4. The pharmaceutical composition of claim 3, wherein the immunogenic fragment of RAGE comprises the amino acid sequence SEQ ID NO:

5, or a conservative variant thereof.

20. A method of treating Alzheimer'"'"'s disease in a subject, comprising administering to the subject the pharmaceutical composition of claim 1.

5. A method of stabilizing a polypeptide antigen for production of an oral vaccine, the method comprising complexing the polypeptide antigen with an amyloid beta (Aβ

) polyeptide.

6. The method of claim 5, wherein the polypeptide antigen is an immunogenic fragment of receptor for advanced glycation endproducts (RAGE) that can bind Aβ

₄₂.

7. The method of claim 6, wherein the immunogenic fragment of RAGE comprises an amino acid sequence of at least 20 amino acids having at least 95% sequence identity to SEQ ID NO:

2.

8. The method of claim 7, wherein the immunogenic fragment of RAGE comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:

5.

9. The method of claim 8, wherein the immunogenic fragment of RAGE comprises the amino acid sequence SEQ ID NO:

5, or a conservative variant thereof.

10. The method of claim 5, wherein the Aβ

polypeptide is Aβ

₄₂ and comprises the amino acid sequence SEQ ID NO;

1, or a conservative variant thereof.

11. The method of claim 5, wherein the Aβ

polypeptide consists of the amino acid sequence SEQ ID NO;

1 and the polypeptide antigen consist of the amino acid sequence SEQ ID NO;

5.

12. A method of provoking an immune response in a lymphocyte, comprising contacting the lymphocyte with an immunogenic polypeptide complex of amyloid beta 42 (Aβ

₄₂) polypeptide and an immunogenic fragment of RAGE, wherein the immunogenic fragment of RAGE can bind Aβ

₄₂.

13. The method of claim 12, wherein the immunogenic fragment of RAGE comprises an amino acid sequence of at least 20 amino acids having at least 95% sequence identity to SEQ ID NO:

2.

14. The method of claim 13, wherein the immunogenic fragment of RAGE comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:

5,

15. The method of claim 14, wherein the immunogenic fragment of RAGE comprises the amino acid sequence SEQ ID NO:

5, or a conservative variant thereof.

16. The method of claim 12, wherein the lymphocyte is in a human subject.

17. The method of claim 12, wherein the lymphocyte is in a non-human subject.

18. The method of claim 12, wherein the lymphocyte is ex vivo.

19. The method of claim 12, wherein the immunogenic polypeptide complex is in a pharmaceutically acceptable carrier.