Efficient mucosal vaccination mediated by the neonatal Fc receptor

Patent metadata

Field	Value
Publication number	US-9238683-B2
Application number	US-93231011-A
Country	US
Kind code	B2
Filing date	Feb 23, 2011
Priority date	Feb 23, 2011
Publication date	Jan 19, 2016
Grant date	Jan 19, 2016

Abstract

The present invention relates to methods and compositions for enhancing delivery of vaccine antigens to the mucosal epithelium, the composition comprising an antigen from an infectious agent fused with an Fc fragment of an immunoglobulin recognized by the neonatal receptors (FcRn). The composition is effective in eliciting a protective long-term memory T cell immune response against infection at a distant mucosal site.

First claim

What is claimed is:

1. A vaccine comprising fusion protein comprising an Fc fragment comprising the hinge region, a CH2 domain and a CH3 domain of an immunoglobulin wherein C1q motif has been mutated such that it renders the fragment non-lytic, wherein said Fc fragment is fused at the amino-terminal to a desired antigen, wherein said antigen is Herpes simplex virus type-2 gD protein.

2. The vaccine of claim 1 , wherein said vaccine protects against infection at a mucosal site distant and different from the site of vaccine administration.

3. The vaccine of claim 1 , wherein said vaccine is capable of promoting and sustaining antigen specific plasma cells in a subject for at least 6 months after vaccination.

4. The vaccine of claim 1 , wherein said mucosal epithelium is chosen from the group consisting of lungs, intestines, colon, nasal tissue, vaginal tissue.

5. The vaccine of claim 1 , wherein said subject is animal or human.

6. The vaccine of claim 1 , further comprising an adjuvant.

7. The vaccine of claim 6 , wherein said adjuvant is CpG.

8. A composition comprising a complex comprising the vaccine of claim 1 bound to FcRn.

9. A composition comprising a fusion protein comprising
an Fc fragment, said Fc fragment comprising the hinge region, a CH2 domain wherein C1q motif has been mutated such that it renders the fragment non-lytic, and a CH3 domain of an immunoglobulin and wherein said Fc fragment is fused at the amino-terminal end to an antigen of interest, wherein said antigen is a pathogenic antigen or allergen.

10. The composition of claim 9 , wherein said pathogenic antigen is chosen from the group consisting of viruses, bacteria, parasites, or fungi.

11. The composition of claim 10 , wherein said virus antigen is chosen from the group consisting of Herpes simplex virus type 2 gD protein, HIV Gag(p24), HIV gp120, influenza HA, influenza NA, influenza M2, respiratory syncytia virus F protein, respiratory syncytia virus G protein, and human papilloma virus protein.

12. The composition of claim 10 , wherein said bacterial antigen is chosen from the group consisting of mycobacterium tuberculosis Ag85B, mycobacterium tuberculosis ESAT6 , Streptococcus pneumonia PspA, Streptococcus pneumonia PsaA, and Streptococcus pneumonia CPbA.

13. An immunogenic composition comprising the composition of claim 9 .

14. The immunogenic composition of claim 13 further comprising an adjuvant.

15. The immunogenic composition of claim 14 wherein said adjuvant is CpG.

16. A composition comprising a fusion protein comprising the hinge region, a CH2 domain wherein C1q motif has been mutated such that it renders the fragment non-lytic, a CH3 domain and excluding a CH1 domain of an immunoglobulin, wherein said Fc fragment is fused at the amino-terminal end to an antigen, wherein said antigen is a pathogenic antigen or an allergen.

17. A method for stimulating a mucosal T cell immune response in a subject comprising administering an effective amount of the vaccine of claim 1 .

18. The method of claim 17 further comprising administering an adjuvant with said vaccine.

19. The method of claim 18 wherein said adjuvant is CpG.

20. A method for transporting the vaccine according to claim 1 across a mucosal barrier said method comprising administering said vaccine to a mucosal epithelia.

21. The method of claim 20 wherein said mucosal barrier is the respiratory mucosal barrier and said administration is intranasal.

22. The method of claim 20 further comprising administering an adjuvant with said fusion protein.

23. The method of claim 21 wherein said adjuvant is CpG.

24. A method for inducing an antibody and cellular immune response at a mucosal and systemic site against an antigen of interest wherein said antigen is HSV-2 gD, said method comprising administering the vaccine of claim 1 to a mucosal epithelium.

25. The method of claim 24 further comprising administering an adjuvant with said vaccine.

26. The method of claim 25 wherein said adjuvant is CpG.

27. A method for stimulating a mucosal T cell immune response in a subject comprising administering an effective amount of a fusion protein comprising Fc fragment consisting essentially of the hinge region, a CH2 domain and a CH3 domain of an immunoglobulin wherein C1q motif has been mutated such that it renders the fragment non-lytic, fused at the amino-terminal to an antigen of interest, wherein said antigen is a pathogenic antigen or allergen, said administration being to a mucosal epithelium.

28. The method of claim 27 further comprising administering an adjuvant with said fusion protein.

29. The method of claim 28 wherein said adjuvant is CpG.

30. A method for mucosal delivery of an antigen, wherein said antigen is a pathogenic antigen or an allergen, said method comprising fusing said antigen to Fc fragment comprising the hinge region, a CH2 domain wherein C1q motif has been mutated such that it renders the fragment non-lytic, and a CH3 domain of an immunoglobulin, wherein said Fc fragment is fused at the amino-terminal end to said antigen to create a fusion protein, and administering said fusion protein composition to a mucosal epithelium.

31. The method of claim 30 wherein said antigen is HSV-2 gD.

32. The method of claim 30 wherein said pathogenic antigen is chosen from the group consisting of viruses, bacteria, parasites, or fungi.

33. The method of claim 32 wherein said virus antigen is chosen from the group consisting of herpes simplex virus type 2 gD protein, HIV Gag(p24), HIV gp120, influenza HA, influenza NA, influenza M2, respiratory syncytia virus F protein, respiratory syncytia virus G protein, and human papilloma virus protein.

34. The method of claim 32 wherein said bacterial antigen is chosen from the group consisting of mycobacterium tuberculosis Ag85B, mycobacterium tuberculosis ESAT6 , Streptococcus pneumonia PspA, Streptococcus pneumonia PsaA, and Streptococcus pneumonia CPbA.

Assignees

• Zhu Xiaoping
• Ye Lilin
• Lu Li
• Univ Maryland

Inventors

• Zhu Xiaoping
• Ye Lilin
• Lu Li

Classifications

• C07K14/005

  from viruses · CPC title

• C07K14/3156

  from Streptococcus pneumoniae (Pneumococcus) (Streptokinase C07K14/3153) · CPC title

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title

• A61K39/21

  Retroviridae, e.g. equine infectious anemia virus · CPC title

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title