Aluminum based adjuvants for tolerogenic vaccination

Patent metadata

Field	Value
Publication number	US-10940200-B2
Application number	US-201615763739-A
Country	US
Kind code	B2
Filing date	Sep 28, 2016
Priority date	Sep 28, 2015
Publication date	Mar 9, 2021
Grant date	Mar 9, 2021

Abstract

The present invention provides methods of modulating an immunological disorder or an immune response. The methods include administering to a subject or a cell an effective amount of an autoimmune antigen and an anti-inflammatory cytokine included in an aluminum-based carrier. Compositions including an autoimmune antigen and an anti-inflammatory cytokine included in an aluminum-based carrier are also provided.

First claim

That which is claimed is:

1. A method of treating multiple sclerosis comprising administering to a subject or a cell an effective amount of an autoimmune antigen and interferon alpha or interferon beta in an aluminum-based carrier; wherein the autoimmune antigen is selected from the group consisting of myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), myelin-associated oligodendrocytic basic protein and cardiac myosin, or portions thereof, and wherein the autoimmune antigen and the interferon alpha or interferon beta are not covalently linked.

2. The method of claim 1 , wherein the autoimmune antigen is an encephalitogenic determinant portion of an autoimmune antigen selected from the group consisting of myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), myelin-associated oligodendrocytic basic protein and cardiac myosin, or portions thereof.

3. The method of claim 2 , wherein the encephalitogenic determinant portion of the MBP, PLP, MOG, myelin-associated oligodendrocytic basic protein or cardiac myosin is (1) an amino acid sequence encoded by a nucleic acid sequence encoding an encephalitogenic determinant portion of the MBP, PLP, MOG, myelin-associated oligodendrocytic basic protein or cardiac myosin, or (2) an amino acid sequence encoded by a nucleic acid sequence that hybridizes with the complement of the nucleic acid sequence of (1) under stringent conditions as represented by hybridization conditions of 0.5M NaHPO 4 , 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65° C. and wash conditions of 0.1×SSC/0.1% SDS at 68° C.

4. The method of claim 1 , wherein the autoimmune antigen and the interferon alpha or interferon beta are non-covalently linked.

5. The method of claim 1 , wherein said administering step is carried out in vivo.

6. The method of claim 1 , wherein said administering step is carried out ex vivo.

7. A method of eliciting a tolerogenic response comprising administering to a subject or a cell an effective amount of an autoimmune antigen and interferon alpha or interferon beta in an aluminum-based carrier; wherein the autoimmune antigen is selected from the group consisting of myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), myelin-associated oligodendrocytic basic protein and cardiac myosin, or portions thereof, and wherein the autoimmune antigen and the interferon alpha or interferon beta are not covalently linked.

8. The method of claim 7 , wherein the tolerogenic response is an active tolerance mechanism.

9. The method of claim 8 , wherein the tolerogenic response is a sustained tolerogenic response.

10. The method of claim 7 , wherein the tolerogenic response is an antigen-specific tolerogenic response without inhibition of adaptive immunity.

11. The method of claim 7 , wherein the autoimmune antigen is an encephalitogenic determinant portion of an autoimmune antigen selected from the group consisting of myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), myelin-associated oligodendrocytic basic protein and cardiac myosin, or portions thereof.

12. The method of claim 7 , wherein the encephalitogenic determinant portion of the MBP, PLP, MOG, myelin-associated oligodendrocytic basic protein or cardiac myosin is (1) an amino acid sequence encoded by a nucleic acid sequence encoding an encephalitogenic determinant portion of the MBP, PLP, MOG, myelin-associated oligodendrocytic basic protein or cardiac myosin, or (2) an amino acid sequence encoded by a nucleic acid sequence that hybridizes with the complement of the nucleic acid sequence of (1) under stringent conditions as represented by hybridization conditions of 0.5M NaHPO 4 , 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65° C. and wash conditions of 0.1×SSC/0.1% SDS at 68° C.

13. The method of claim 7 , wherein the autoimmune antigen and the interferon alpha or interferon beta are non-covalently linked.

14. The method of claim 7 , wherein said administering step is carried out in vivo.

15. The method of claim 7 , wherein said administering step is carried out ex vivo.

16. A method of treating multiple sclerosis in a subject in need thereof, comprising administering to the subject an effective amount of an autoimmune antigen and IFN-β in an aluminum-based adjuvant; wherein the autoimmune antigen is selected from the group consisting of myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), myelin-associated oligodendrocytic basic protein and cardiac myosin, or portions thereof, and wherein the autoimmune antigen and IFN-β are not covalently linked.

17. A method of treating multiple sclerosis comprising administering to a subject or a cell an effective amount of a composition comprising a interferon alpha or interferon beta in an aluminum-based carrier, wherein the composition does not comprise an autoimmune antigen.

18. The method of claim 17 , wherein said administering step is carried out in vivo.

19. The method of claim 17 , wherein said administering step is carried out ex vivo.

20. A method of eliciting a tolerogenic response comprising administering to a subject or a cell an effective amount of a composition comprising a interferon alpha or interferon beta in an aluminum-based carrier, wherein the composition does not comprise an autoimmune antigen.

21. The method of claim 20 , wherein the tolerogenic response is an active tolerance mechanism.

22. The method of claim 20 , wherein the tolerogenic response is a sustained tolerogenic response.

23. The method of claim 20 , wherein the tolerogenic response is an antigen-specific tolerogenic response without inhibition of adaptive immunity.

24. The method of claim 20 , wherein said administering step is carried out in vivo.

25. The method of claim 20 , wherein said administering step is carried out ex vivo.

26. A method of treating multiple sclerosis in a subject in need thereof, comprising administering to the subject an effective amount of IFN-β in an aluminum-based adjuvant.

Assignees

• Univ East Carolina

Inventors

• Mannie Mark D

Classifications

• A61K39/0008

  Antigens related to auto-immune diseases; Preparations to induce self-tolerance · CPC title

• A61K2039/577

  tolerising response · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K47/02

  Inorganic compounds · CPC title

• A61K2039/55505

  Inorganic adjuvants · CPC title