TH1/TH2 polarizing vaccines

Patent metadata

Field	Value
Publication number	US-9795661-B2
Application number	US-91455510-A
Country	US
Kind code	B2
Filing date	Oct 28, 2010
Priority date	Nov 16, 2009
Publication date	Oct 24, 2017
Grant date	Oct 24, 2017

Abstract

The present invention relates to recombinant chimeric molecules that are capable of providing T cell receptor (TCR) interaction and costimulation for activation and differentiation of pathogen-specific T cells toward effector T helper 1 (Th1) or T helper 2 (Th2) cells. The chimera may capable of elicit antibodies against pathogen-specific B cell epitope(s). The present invention also relates method of using these chimeric molecules in whole or as a component of a vaccine.

First claim

The invention claimed is:

1. A malaria vaccine comprises a chimeric molecule, wherein said chimeric molecule comprising:
a) an immunoglobulin scaffold, wherein said immunoglobulin scaffold comprising a domain specific for binding to a protein on an antigen presenting cell;
b) a costimulatory domain linked to a heavy chain of said immunoglobulin scaffold; and
c) a circumsporrozoite protein-specific (CSP-specific) T cell epitope linked to a c-terminus of a light chain of said immunoglobulin scaffold.

2. The malaria vaccine of claim 1 , wherein said chimeric molecule further comprising at least one malaria-specific B cell epitope linked to the C-terminus of said heavy chain of said immunoglobulin scaffold.

3. The malaria vaccine of claim 1 , wherein said immunoglobulin scaffold is a humanized immunoglobulin.

4. The malaria vaccine of claim 1 , wherein said immunoglobulin scaffold comprising at least one domain of an immunoglobulin Ig.G.

5. The malaria vaccine of claim 4 , wherein said immunoglobulin is IgG1, IgG2, IgG3, or IgG4.

6. The malaria vaccine of claim 1 , wherein said antigen presenting cell is selected from the group consisting of dendritic cells, Langerhans cells, B cells, monocytes, macrophages, endothelial cells, and granulocytes.

7. The malaria vaccine of claim 1 , wherein said antigen presenting cell is a dendritic cell.

8. The malaria vaccine of claim 7 , wherein said protein on said antigen presenting cell is CD205.

9. The malaria vaccine of claim 1 , wherein said costimulatory domain is linked to C-terminus of said heavy chain of said immunoglobulin.

10. The malaria vaccine of claim 1 , wherein said costimulatory domain is selected from the group consisting of B7.1 (CD80), B7.2 (CD86), interleukin 2, and Interleukin 12.

11. The malaria vaccine of claim 1 , wherein said costimulatory domain is B7.1.

12. The malaria vaccine of claim 1 , wherein said costimulatory domain is selected from the group consisting of interleukin-4, interleukin-5, interleukin-6, interleukin-10, interleukin-13.

13. The malaria vaccine of claim 1 , wherein said costimulatory domain comprising interleukin-4.

14. The malaria vaccine of claim 1 , wherein said T cell epitope is a CD4 T cell epitope or a CD8 T cell epitope.

15. The malaria vaccine of claim 2 , wherein said malaria-specific B cell epitope comprising at least one immunogenic polypeptide selected from antigens consisting of circumsporrozoite protein (CSP), thrombospondin related adhesive protein/sporozoites surface protein-2 (TRAP/SSP2), liver stage antigen-1 (LSA1), merozoite surface protein-1 (MSP1), apical membrane antigen-1 (AMA-1).

16. The malaria vaccine of claim 15 , wherein said malaria-specific B cell epitope is linked to said C-terminus of said heavy chain of said immunoglobulin scaffold by a glycine linker.

17. The malaria vaccine of claim 16 , wherein said costimulatory domain is linked to said malaria-specific B cell epitope.

18. An immunogenic composition, comprising the malaria vaccine of claim 1 .

19. The malaria vaccine of claim 17 , wherein said costimulatory domain is linked to said pathogen-specific B cell epitope by a glycine linker.

Assignees

• Casares Sofia A
• Richie Thomas L
• Brumeanu Teodor D
• Us Navy

Inventors

• Casares Sofia A
• Richie Thomas L
• Brumeanu Teodor D

Classifications

• A61P31/20

  for DNA viruses · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P31/16

  for influenza or rhinoviruses · CPC title

• A61P33/02

  Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis · CPC title

• A61P31/04

  Antibacterial agents · CPC title