Peptide vaccine formulations and use thereof for inducing an immune response

1. An immunogenic composition for inducing an immune response to a peptide antigen in a subject, the immunogenic composition comprising polymer nanoparticles, the polymer nanoparticles comprising:

a first polymer linked to a conjugate by an electrostatic interaction, the conjugate comprising the peptide antigen linked to a peptide tag; and

an adjuvant; and

wherein

the electrostatic interaction is between the first polymer and the peptide tag;

the first polymer comprises a net positive charge and the peptide tag comprises a net negative charge at pH 7.4;

the peptide antigen from 8-12 amino acids in length or from 29-35 amino acids in length;

the peptide antigen and the conjugate are soluble in phosphate buffered saline at pH 7.4;

the peptide tag is C-terminal to the peptide antigen in the conjugate;

the peptide tag comprises 5 to 15 amino acids;

the adjuvant is linked to the first polymer through an amide bond;

the adjuvant is a toll-like receptor 7/8 agonist;

a ratio of the adjuvant to monomer of the first polymer is from 1:100 to 1:10 mol/mol; and

the polymer nanoparticles enter immune cells under physiological conditions to induce the immune response to the peptide antigen in the subject.

2. The immunogenic composition of claim 1 , wherein the peptide antigen is linked to the peptide tag by a linker.

3. The immunogenic composition of claim 2 , wherein the linker is a cathepsin-cleavable peptide linker.

4. The immunogenic composition of claim 1 , wherein the peptide tag comprises from 1 to 5 aromatic amino acids.

5. The immunogenic composition of claim 4 , wherein the aromatic amino acid is selected from tryptophan, phenylanine, tyrosine, histidine or glutamic acid gamma-benzyl ester.

6. The immunogenic composition of claim 1 , wherein the peptide tag consists of 10 glutamate residues.

7. The immunogenic composition of claim 1 , wherein the ratio of the net charge of the first polymer to the net charge of the conjugate in the polymer nanoparticle at pH 7.4 is from about 20:1 to about 1:20 mol/mol.

8. The immunogenic composition of claim 1 , wherein the first polymer is a poly(ethylenimine) polymer, a poly(lysine) polymer, or a poly(arginine) polymer.

9. The immunogenic composition of claim 1 , wherein:

(A) the first polymer is a poly(lysine)-based polymer, and a positive to negative charge ratio of the net charge of the conjugate to the net charge of the first polymer is from about 5:1 to about 2:1 mol/mol, or from about 1:10 to about 1:20 mol/mol;

(B) the first polymer is a poly(arginine)-based polymer, and a positive to negative charge ratio of the net charge of the conjugate to the net charge of the first polymer is from about 5:1 to about 2:1 mol/mol, or from about 1:10 to about 1:20 mol/mol; or

(C) the first polymer is a poly(ethylenimine)-based polymer, and a positive to negative charge ratio of the net charge of the conjugate to the net charge of the first polymer is from about 1:5 to about 1:10 mol/mol.

10. The immunogenic composition of claim 1 , further comprising a second polymer, wherein the second polymer is a poly(anionic) polymer that comprises a net electrostatic charge that is opposite to that of the first polymer.

11. The immunogenic composition of claim 10 , wherein

a positive to negative charge ratio of the net charge of the conjugate and the second polymer to the net charge of the first polymer is from about 1:5 to about 1:10, or about 2:1 mol/mol.

12. The immunogenic composition of claim 1 , wherein:

the first polymer is poly(lysine) and a ratio of adjuvant to monomer of the first polymer is from 1:100 to 1:10 mol/mol; or

the first polymer is poly(ethlyenimine) and a ratio of adjuvant to monomer of the first polymer is from 1:100 to 1:10 mol/mol.

13. The immunogenic composition of claim 1 , wherein the first and/or second polymer comprises a plurality of monomers comprising from 5 monomers to 500 monomers.

14. The immunogenic composition of claim 1 , wherein the antigen is a tumor associated peptide antigen, a viral peptide antigen, a bacterial peptide antigen, or a protozoan peptide antigen.

15. The immunogenic composition of claim 1 , wherein the first polymer linked to the conjugate, and the adjuvant, and, if present, the second polymer, self-assemble into the polymer nanoparticles in phosphate buffered saline, pH 7.4.

16. The immunogenic composition of claim 1 , wherein the polymer nanoparticles are from about 20 to about 200 nm in diameter.

17. The immunogenic composition of claim 1 , wherein the polymer nanoparticles comprise from about 5 to about 20 different peptide antigen conjugates.

18. The immunogenic composition of claim 1 , wherein the polymer nanoparticles are polyplex nanoparticles.

19. A method of inducing an immune response in a subject to a peptide antigen, comprising administering an effective amount of the immunogenic composition of claim 1 to a subject to induce the immune response.

20. The method of claim 19 , comprising administering the immunogenic composition to a target location in the subject.

21. The method of claim 19 , comprising intravenous administration of the immunogenic composition to the subject.

22. The immunogenic composition of claim 7 , wherein the ratio of the net charge of the first polymer to the net charge of the conjugate in the polymer nanoparticle is from 4:1 to 6:1 mol/mol.

23. The immunogenic composition of claim 22 , wherein the ratio of the net charge of the first polymer to the net charge of the conjugate in the polymer nanoparticle is about 5:1 mol/mol.

24. The immunogenic composition of claim 1 , wherein the ratio of adjuvant to monomer of the first polymer is from 1:20 to 1:10 mol/mol.

25. The immunogenic composition of claim 12 , wherein:

the first polymer is poly(lysine) and the ratio of adjuvant to monomer of the first polymer is from 1:20 to 1:10 mol/mol; or

the first polymer is poly(ethlyenimine) and the ratio of adjuvant to monomer of the first polymer is from 1:100 to 1:20 mol/mol.

26. The immunogenic composition of claim 24 , wherein:

the first polymer is poly(lysine) and the ratio of adjuvant to monomer of the first polymer is about 1:20 mol/mol; or

the first polymer is poly(ethlyenimine) and the ratio of adjuvant to monomer of the first polymer is about 1:40 mol/mol.

27. The immunogenic composition of claim 1 , wherein the peptide antigen is from a tumor associated antigen or a tumor neoantigen comprising an amino acid mutation not present in non-cancerous cells and wherein the peptide antigen comprises 10-20 amino acids flanking the amino acid mutation of the tumor associated antigen or a tumor neoantigen.

28. The immunogenic composition of claim 1 , wherein the peptide tag comprises from 5 to 15 aspartic acid or glutamic acid residues.