Synthetic long peptides (SLP) for therapeutic vaccination against hepatitis B virus infection
The present invention relates to the fields of medicine and immunology. In particular, it relates to novel peptides that may be used in the treatment and/or prevention of a Hepatitis B viral infection and/or an Hepatitis B related disease or condition.
1. An immunogenic pharmaceutical composition comprising:
(a) a peptide of at least 30 and at most 40 amino acids in length and comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 51-79, 1142-1145 and 1468-1471,
(b) an immune-stimulating amount of at least one pharmaceutically acceptable adjuvant selected from the group consisting of a human toll-like receptor ligand and/or agonist, Montanide ISA-51, Montanide ISA-720, dsRNA, cyclic dinucleotides (CDNs), Muramyl dipeptide (MDP), a tetanus toxin derived peptide, Interferon alpha (INFα), and combinations thereof.
2. The composition according to claim 1 , further comprising an additional peptide.
3. The composition according to claim 1 , wherein the peptide comprises an amino acid sequence of any of the proteins selected from the group consisting of HBV polymerase, HBV core protein, HBV X-protein and HBV large surface protein.
4. The composition according to claim 1 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 51-53, 55, 57, 60, 63, 64, 66, 68, 71, 72, 74-78, 1142, 1145, 1468-1471.
5. The composition according to claim 1 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 55, 60, 63, 64, 68, 71, 75, 77, 1142 and 1469.
6. The composition according to claim 1 , wherein the peptide further comprises a covalently linked functional group, an oligonucleotide conjugate, a sugar chain or glycan, or combinations thereof.
7. The composition according to claim 6 , wherein the covalently linked functional group is a fluorinated group.
8. An immunogenic pharmaceutical composition comprising:
(a) a polynucleotide encoding a peptide at least 30 and at most 40 amino acids in length, wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 51-79, 1142-1145 and 1468-1471;
(b) an immune-stimulating amount of at least one pharmaceutically acceptable adjuvant selected from the group consisting of a human toll-like receptor ligand and/or agonist, Montanide ISA-51, Montanide ISA-720, dsRNA, cyclic dinucleotides (CDNs), Muramyl dipeptide (MDP), a tetanus toxin derived peptide, Interferon alpha (IFNα), and combinations thereof.
9. The composition according to claim 8 , further comprising the peptide.
10. The composition according to claim 8 , wherein the peptide comprises an amino acid sequence of any of the proteins selected from the group consisting of HBV polymerase, HBV core protein, HBV X-protein and HBV large surface protein.
11. The composition according to claim 8 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 51-53, 55, 57, 60, 63, 64, 66, 68, 71, 72, 74-78, 1142, 1145, and 1468-1471.
12. The composition according to claim 8 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 55, 60, 63, 64, 68, 71, 75, 77, 1142 and 1469.
13. The composition according to claim 9 , wherein the peptide of the composition further comprises a covalently linked functional group, an oligonucleotide conjugate, a sugar chain or glycan, or combinations thereof.
14. The composition according to claim 13 , wherein the covalently linked functional group is a fluorinated group.
15. The composition according to claim 1 , further comprising PSA, 2-aminoisobutyric acid (Abu), a DC pulse cassette, or combinations thereof.
16. The composition according to claim 1 , wherein the human toll-like receptor ligand and/or agonist is selected from the group consisting of Gram positive bacterial glycolipid, LPS, LPA, LTA, fimbriae, an outer membrane protein, a heat shock protein, Mycobacterial lipoarabinomannans, dsRNA, poly(I:C), Gram negative bacterial glycolipid, a viral coat protein, a viral envelope protein, taxol and/or derivative thereof, hyaluronan containing oligosaccharides and fibronectins, bacterial flagellae, flagellin, Mycobacterial lipoproteins, group B Streptococcus heat labile soluble factor, a Staphylococcus modulin, imidazoquinolines, imiquimod and/or derivative thereof, resiquimod and/or derivative thereof, unmethylated CpG DNA, chromatin-IgG complexes, IC31, IMSAVAC, pam3cys and/or derivative thereof, poly-ICLC, and CpG oligodeoxynucleotides (CpG-ODNs).
17. The composition according to claim 8 , further comprising PSA, 2-aminoisobutyric acid (Abu), a DC pulse cassette, or combinations thereof.
18. The composition according to claim 8 , wherein the human toll-like receptor ligand and/or agonist is selected from the group consisting of Gram positive bacterial glycolipid, LPS, LPA, LTA, fimbriae, an outer membrane protein, a heat shock protein, Mycobacterial lipoarabinomannans, dsRNA, poly(I:C), Gram negative bacterial glycolipid, a viral coat protein, a viral envelope protein, taxol and/or derivative thereof, hyaluronan containing oligosaccharides and fibronectins, bacterial flagellae, flagellin, Mycobacterial lipoproteins, group B Streptococcus heat labile soluble factor, a Staphylococcus modulin, imidazoquinolines, imiquimod and/or derivative thereof, resiquimod and/or derivative thereof, unmethylated CpG DNA, chromatin-IgG complexes, IC31, IMSAVAC, pam3cys and/or derivative thereof, poly-ICLC, and CpG oligodeoxynucleotides (CpG-ODNs).
19. The composition according to claim 1 , wherein the pharmaceutically acceptable adjuvant is Montanide ISA-51.
20. The composition according to claim 8 , wherein the pharmaceutically acceptable adjuvant is Montanide ISA-51.
21. An immunogenic pharmaceutical composition comprising a peptide of at least 30 and at most 40 amino acids in length and comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 51-79, 1142-1145 and 1468-1471, wherein the peptide further comprises a covalently linked functional group, an oligonucleotide conjugate, a sugar chain or glycan, or combinations thereof.
22. The composition according to claim 21 , wherein the covalently linked functional group is a fluorinated group.
23. The composition according to claim 21 , further comprising an immune-stimulating amount of at least one pharmaceutically acceptable adjuvant.
24. The composition according to claim 16 , wherein the pam3cys and/or derivative thereof comprises a pam3cys lipopeptide or derivative thereof.
25. The composition according to claim 18 , wherein the pam3cys and/or derivative thereof comprises a pam3cys lipopeptide or derivative thereof.