Glycoconjugate vaccines

1. A method of preparing a glycated peptide conjugate, the method comprising:

obtaining a population of polysaccharides;

treating the population of polysaccharides to create a treated population of polysaccharides having an average molecular weight of 10-20 kDa;

contacting the treated population of polysaccharides with polypeptides comprising a plurality of repeating peptide units linked together by cleavable moieties, wherein each peptide unit consists of:

(i) an MHC-II binding sequence of 20 amino acids or fewer, wherein none of the amino acids are lysine;

(ii) one lysine residue at the C terminal end; and

(iii) one or more amino acids linking the MHC-II binding sequence to the lysine residue, wherein none of the amino acids are lysine;

under conditions sufficient to link the treated polysaccharides directly to the lysine residues, thereby preparing the glycated peptide conjugate.

2. The method of claim 1 , further comprising:

providing a biocompatible nanoparticle; and

linking the N terminal end of the glycated peptide conjugate to the biocompatible nanoparticle via a cleavable linker.

3. The method of claim 1 , wherein the population of polysaccharides is from a pathogen selected from the group consisting of viruses, bacteria, protozoa, and fungi.

4. The method of claim 1 , wherein the population of polysaccharides is from a tumor.

5. The method of claim 1 , wherein treating the population of polysaccharides comprises exposing the polysaccharide to ozonolysis or enzymatic digestion.

6. The method of claim 2 , wherein the cleavable linker is an acid-labile sequence.

7. The method of claim 2 , wherein the cleavable linker is a protease recognition sequence.

8. The method of claim 1 , wherein the glycated peptide conjugate comprises peptide units with the same MHC-II binding sequence.

9. The method of claim 1 , wherein the glycated peptide conjugate comprises peptide units with different MHC-II binding sequences.

10. A glycated peptide conjugate comprising a polypeptide comprising a plurality of repeating peptide units linked together by cleavable moieties, wherein each peptide unit consists of:

(i) an MHC-II binding sequence of 20 amino acids or fewer, wherein none of the amino acids are lysine;

(ii) one lysine residue at the C terminal end;

(iii) one or more amino acids linking the MHC-II binding sequence to the lysine residue, wherein none of the amino acids are lysine; and

(iv) a polysaccharide having an average molecular weight of 10-20 kDa linked directly to the lysine residue.

11. The glycated peptide conjugate of claim 10 , wherein the glycated peptide conjugate is linked to a biocompatible nanoparticle at the N terminal end of the glycated peptide conjugate, via a cleavable linker.

12. The glycated peptide conjugate of claim 10 , wherein the polysaccharide is from a pathogen selected from the group consisting of viruses, bacteria, protozoa, and fungi.

13. The glycated peptide conjugate of claim 10 , wherein the polysaccharide is from a tumor.

14. The glycated peptide conjugate of claim 10 , wherein the cleavable moiety is an acid-labile sequence.

15. The glycated peptide conjugate of claim 10 , wherein the cleavable moiety is a protease recognition sequence.

16. The glycated peptide conjugate of claim 10 , wherein the plurality of peptide units comprise the same MHC-II binding sequence.

17. The glycated peptide conjugate of claim 10 , wherein the plurality of peptide units comprise a plurality of MHC-II binding sequences.

18. A method of inducing an immune response in a subject, the method comprising administering a therapeutically effective amount of the glycated peptide conjugate of claim 10 .

19. A composition comprising the glycated peptide conjugate of claim 10 , in a pharmaceutically acceptable carrier.

20. A glycated peptide conjugate comprising a peptide unit consisting of:

(i) an MHC-II binding sequence of 20 amino acids or fewer, wherein none of the amino acids are lysine;

(ii) a lysine residue at the C terminal end;

(iii) one or more amino acids linking the MHC-II binding sequence to the lysine residue, wherein none of the amino acids are lysine; and

(iv) a polysaccharide having an average molecular weight of 10-20 kDa linked directly to the lysine residue.

21. The glycated peptide conjugate of claim 20 , wherein the glycated peptide conjugate is linked to a biocompatible nanoparticle at the N terminal end of the glycated peptide conjugate, via a cleavable linker.

22. The glycated peptide conjugate of claim 20 , wherein the polysaccharide is from a pathogen selected from the group consisting of viruses, bacteria, protozoa, and fungi.

23. The glycated peptide conjugate of claim 20 , wherein the polysaccharide is from a tumor.

24. The method of claim 21 , wherein the cleavable linker is an acid-labile sequence.

25. The method of claim 21 , wherein the cleavable linker is a protease recognition sequence.

26. A method of inducing an immune response in a subject, the method comprising administering a therapeutically effective amount of the glycated peptide conjugate of claim 20 .

27. A composition comprising the glycated peptide conjugate of claim 20 , in a pharmaceutically acceptable carrier.

28. The glycated peptide conjugate of claim 10 , wherein the one or more amino acids linking the MHC-II binding sequence to the lysine residue comprise an amino acid sequence of glutamate-serine-glycine.

29. The glycated peptide conjugate of claim 10 , wherein the polysaccharide has an average molecular weight of 10-15 kDa.

30. The glycated peptide conjugate of claim 10 , wherein the polysaccharide has an average molecular weight of 10 kDa.

31. The glycated peptide conjugate of claim 10 , wherein the polysaccharide has an average molecular weight of 15 kDa.

32. The glycated peptide conjugate of claim 20 , wherein the one or more amino acids linking the MHC-II binding sequence to the lysine residue comprise an amino acid sequence of glutamate-serine-glycine.

33. The glycated peptide conjugate of claim 20 , wherein the polysaccharide has an average molecular weight of 10-15 kDa.

34. The glycated peptide conjugate of claim 20 , wherein the polysaccharide has an average molecular weight of 10 kDa.

35. The glycated peptide conjugate of claim 20 , wherein the polysaccharides have polysaccharide has an average molecular weight of 15 kDa.

36. The method of claim 1 , wherein the cleavable moiety is an acid-labile sequence.

37. The method of claim 1 , wherein the cleavable moiety is a protease recognition sequence.

38. The method of claim 4 , wherein the polysaccharide is from a glycoprotein selected from the group consisting of Mucin-1 (MUC-1), NER-2/neu, carcino-embryonic antigen (CEA), p53, Sialyl Tn (STn), Globo H, GM2 ganglioside, GD2 ganglioside, and GD3 ganglioside.

39. The method of claim 11 , wherein the cleavable linker is an acid-labile sequence.

40. The method of claim 11 , wherein the cleavable linker is a protease recognition sequence.

41. The glycated peptide conjugate of claim 13 , wherein the polysaccharide is from a glycoprotein selected from the group consisting of Mucin-1 (MUC-1), NER-2/neu, carcino-embryonic antigen (CEA), p53, Sialyl Tn (STn), Globo H, GM2 ganglioside, GD2 ganglioside, and GD3 ganglioside.

42. The glycated peptide conjugate of claim 23 , wherein the polysaccharide is Mucin-1 (MUC-1), NER-2/neu, carcino-embryonic antigen (CEA), p53, Sialyl Tn (STn), Globo H, GM2 ganglioside, GD2 ganglioside, or GD3 ganglioside.