Immunostimulatory method
This invention relates to a method for treating or preventing a disease by raising an innate immune response in a subject, the method comprising administering to the subject an effective amount of a composition comprising a TLR2 moiety in solution, wherein the TLR2 moiety comprises a TLR2 agonist and wherein the disease is not treated or prevented by a humoral or cellular immune response directed against the TLR2 moiety.
1. A method for preventing or treating a respiratory condition associated with one or more viral infectious agents in a subject, the method comprising:
administering to the respiratory tract of the subject a composition comprising a soluble TLR2 moiety comprising a TLR2 agonist and a solubilizing agent that increases the solubility of the TLR2 agonist in polar or aqueous solvents,
thereby preventing or treating the respiratory condition in the subject,
wherein the moiety raises an innate immune response in the subject and does not raise an immune response that is specific for an antigen of the one or more infectious agents,
wherein the composition does not contain a peptide antigen comprising a T-helper epitope, and
wherein the TLR2 agonist is a lipopeptide.
2. The method according to claim 1 , wherein the TLR2 agonist is selected from the group consisting of S-[2,3-bis(palmitoyloxy)propyl]cysteine (Pam 2 Cys), N-palmitoyl-S-[2,3-bis(palmitoyloxy)propyl]cysteine (Pam 3 Cys), S-[2,3-bis(stearoyloxy)propyl]cysteine, S-[2,3-bis(lauroyloxy)propyl]cysteine, and S-[2,3-bis(octanoyloxy)propyl]cysteine.
3. The method according to claim 2 , wherein the TLR2 agonist is Pam 2 Cys.
4. The method according to claim 1 , wherein the soluble TLR2 moiety comprises polyethyleneglycol (PEG) or a polar polypeptide.
5. The method according to claim 4 , wherein the polar polypeptide is selected from the group consisting of R4, K4, H4, E8, branched E8and H8.
6. The method according to claim 4 , wherein the soluble TLR2 moiety comprises polyethyleneglycol (PEG).
7. The method according to claim 1 , wherein the soluble TLR2moiety comprises polyethyleneglycol (PEG) and any one of R4, K4, H4, E8, branched E8 and H8.
8. The method according to claim 1 , wherein the soluble TLR2moiety is R4Pam2Cys.
9. The method according to claim 1 , wherein the soluble TLR2 moiety is PEG-Pam2Cys.
10. The method according to claim 1 , wherein the soluble TLR2 moiety is E8Pam2Cys.
11. The method according to claim 1 , wherein the soluble TLR2 moiety is H8Pam2Cys.
12. The method according to claim 1 , wherein the composition is administered intranasally to the subject.
13. The method according to claim 1 , wherein the virus is Influenza A virus (IAV).
14. The method according to claim 1 , wherein a TLR9 agonist is not administered.
15. The method according to claim 1 , wherein the soluble TLR2 moiety does not comprise a peptide antigen.
16. The method according to claim 1 , wherein the soluble TLR2 moiety does not comprise an antigen.
17. The method according to claim 1 , wherein the soluble TLR2 moiety consists of a TLR2 agonist conjugated to a solubilizing agent.
18. The method according to claim 1 , wherein the soluble TLR2 moiety comprises an antigen that cannot raise a specific immune response to the one or more infectious agents.
19. The method according to claim 8 , wherein R4Pam2Cys has the structure:
20. The method according to claim 5 , wherein H4Pam2Cys has the structure:
21. The method according to claim 11 , wherein H8Pam2Cys has the structure:
22. The method according to claim 10 , wherein E8Pam2Cys has the structure:
23. The method according to claim 5 , wherein branched E8Pam2Cys has the structure:
24. The method according to claim 7 , wherein the soluble TLR2 moiety comprises polyethyleneglycol (PEG) and R4.
25. The method according to claim 24 , wherein R4 is present as R4Pam2Cys.
26. The method according to claim 25 , wherein R4Pam2Cys has the structure:
27. The method according to claim 1 , wherein the subject has already been infected by the one or more viral infectious agents at the time of said administering, and wherein said administering treats the respiratory condition in the subject.
28. The method according to claim 1 , wherein the subject has not yet been infected by the one or more viral infectious agents at the time of said administering, and wherein said administering prevents the respiratory condition in the subject.