HMGB1-derived peptides enhance immune response to antigens
View Patent ↗The invention provides an immunostimulatory peptide containing the amino acid sequence SAFFLFCSE and uses thereof. The invention also provides an immunostimulatory peptide containing the amino acid sequence DPNAPKRPPSAFFLX 1 X 2 X 3 X 4 or derivatives thereof. In one embodiment, when X1 is alanine (A), glycine (G), or valine (V) then X2 is C, X3 is S and X4 is E; wherein when X2 is alanine (A), glycine (G), or valine (V) then X1 is F, X3 is S and X4 is E; wherein when X3 is alanine (A), glycine (G), or valine (V) then X1 is F, X2 is C and X4 is E; or wherein when X4 is alanine (A), glycine (G), or valine (V) then X1 is F, X2 is C and X3 is S.
1. An isolated immunostimulatory peptide comprising the amino acid sequence DPNAPKRPPSAFFLX 1 X 2 X 3 X 4 (SEQ ID NO:9),
wherein the peptide comprises an alpha helix; and
wherein X1 is alanine (A), glycine (G), or valine (V) and X2 is C, X3 is S and X4 is E;
wherein X2 is alanine (A), glycine (G), or valine (V) and X1 is F, X3 is S and X4 is E;
wherein X3 is alanine (A), glycine (G), or valine (V) and X1 is F, X2 is C and X4 is E; or
wherein X4 is alanine (A), glycine (G), or valine (V) and X1 is F, X2 is C and X3 is S.
2. The isolated immunostimulatory peptide of claim 1 , wherein DPNAPKRPPSAFFLX 1 X 2 X 3 X 4 (SEQ ID NO:9) has the amino acid sequence:
a. DPNAPKRPPSAFFLX 1 CSE (SEQ ID NO:10),
b. DPNAPKRPPSAFFLFX 2 SE (SEQ ID NO:11),
c. DPNAPKRPPSAFFLFCX 3 E (SEQ ID NO:12), or
d. DPNAPKRPPSAFFLFCSX 4 (SEQ ID NO:13),
wherein X 1 , X 2 , X 3 and X 4 is alanine (A), glycine (G), or valine (V).
3. The isolated immunostimulatory peptide of claim 1 , wherein the alpha helix produces a circular dichroism profile with negative peaks at about 205-207 nm and/or 222 nm.
4. The isolated immunostimulatory peptide of claim 1 , wherein the peptide induces release of cytokines, wherein the cytokines comprise IFN-γ, IL-12 (p70) and TNF-α.
5. The isolated immunostimulatory peptide of claim 1 , wherein the peptide enhances an antigen-specific cellular immune response or antigen-specific CD8+T cell response.
6. The isolated immunostimulatory peptide of claim 5 , wherein an antigen-specific cellular immune response or antigen-specific CD8 T cell response comprises antigen-specific cytotoxic T-lymphocyte (CTL) response.
7. The isolated immunostimulatory peptide of claim 1 , wherein the peptide induces a Th1-type immune response.
8. The isolated immunostimulatory peptide of claim 1 , wherein the peptide enhances a humoral immune response.
9. The isolated immunostimulatory peptide of claim 8 , wherein the humoral immune response comprises an increased IgG1 isotype.
10. The isolated immunostimulatory peptide of claim 1 , wherein the peptide is a recombinant or synthetic peptide.
11. The isolated immunostimulatory peptide of claim 1 , wherein the peptide is labeled with a biotin, fluorescent tag, a maleimide or a crosslinking agent.
12. The isolated immunostimulatory peptide of claim 1 , wherein the peptide comprises a monomer, dimer, trimer or tetramer.
13. The isolated immunostimulatory peptide of claim 12 , wherein the dimer is a homodimer.
14. The isolated immunostimulatory peptide of claim 12 , wherein the dimer is a heterodimer.
15. The isolated immunostimulatory peptide of claim 1 , wherein sequence of last four amino acids at C-terminus of the peptide peptide maintains immunostimulatory potential or confers greater immunostimulatory potential than naturally occurring FCSE sequence.
16. The isolated immunostimulatory peptide of claim 1 , wherein the peptide functions as an adjuvant to enhance an immune response to peptide or protein antigen.
17. The immunostimulatory peptide of claim 11 , wherein the crosslinking agent is selected from the group consisting of polyalkylene glycol (PAG) and a lipid.
18. The immunostimulatory peptide of claim 17 , wherein the PAG is a polyethylene glycol (PEG).
19. The immunostimulatory peptide of claim 1 , wherein the alpha helix conformation provides a circular dichroism profile that shows negative peaks at about 205-206 nm or 222 nm.