Vaccines for recurrent respiratory papillomatosis and methods of using the same
Provided herein are nucleic acid molecules encoding an HPV antigen. Also provided are vaccines against human papillomavirus (HPV) comprising the nucleic acids, methods of inducing immune responses, and methods for prophylactically and/or therapeutically immunizing individuals against recurrent respiratory papillomatosis (RRP). Pharmaceutical compositions, recombinant vaccines comprising DNA plasmid and live attenuated vaccines are disclosed as well as methods of inducing an immune response to treat or prevent RRP are disclosed.
1. A nucleic acid molecule encoding a human papillomavirus (HPV) antigen, the HPV antigen comprising:
the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 11; or
an amino acid sequence that is at least 95% homologous to SEQ ID NO: 1 or SEQ ID NO: 11.
2. The nucleic acid molecule according to claim 1 , comprising:
a nucleotide sequence at least 95% homologous to SEQ ID NO: 2 or SEQ ID NO: 12;
the nucleotide sequence of SEQ ID NO: 2; or
the nucleotide sequence of SEQ ID NO 12.
3. An expression vector comprising the nucleic acid molecule according to claim 1 .
4. The expression vector of claim 3 comprising a DNA plasmid.
5. The expression vector of claim 3 , comprising the nucleotide sequence of SEQ ID NO: 3.
6. An immunogenic protein comprising:
the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 11, or
an amino acid sequence that is at least 95% homologous to the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 11.
7. A vaccine comprising the expression vector of claim 3 and a pharmaceutically acceptable excipient.
8. A pharmaceutical composition comprising the expression vector of claim 3 and a pharmaceutically acceptable excipient.
9. The pharmaceutical composition according to claim 8 , comprising an adjuvant.
10. The pharmaceutical composition according to claim 9 wherein the adjuvant comprises interleukin-12 (IL12).
11. The pharmaceutical composition according to claim 9 wherein the adjuvant comprises a nucleic acid molecule encoding IL12.
12. The pharmaceutical composition according to claim 11 , wherein the nucleic acid molecule encoding IL12 is an expression vector.
13. A vaccine comprising the immunogenic protein of claim 6 and a pharmaceutically acceptable excipient.
14. A pharmaceutical composition comprising the immunogenic protein of claim 6 and a pharmaceutically acceptable excipient.
15. The pharmaceutical composition according to claim 14 , comprising an adjuvant.
16. The pharmaceutical composition according to claim 15 wherein the adjuvant comprises interleukin-12 (IL12).
17. The pharmaceutical composition according to claim 9 , wherein the adjuvant comprises a nucleic acid molecule comprising a nucleotide sequence encoding the p35 subunit of IL-12, the p40 subunit of IL-12, or both.
18. The pharmaceutical composition according to claim 17 , wherein the nucleotide sequence encoding the p35 subunit of IL12 comprises a nucleotide sequence selected from the group consisting of:
a nucleotide sequence that encodes SEQ ID NO: 6; or
a nucleotide sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO: 6.
19. The pharmaceutical composition according to claim 17 , wherein the nucleotide sequence encoding the p40 subunit of IL12 comprises a nucleotide sequence selected from the group consisting of:
a nucleotide sequence that encodes SEQ ID NO: 8; or
a nucleotide sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO: 8.
20. The pharmaceutical composition according to claim 17 , wherein the nucleotide sequence encoding IL12 comprises a nucleotide sequence selected from the group consisting of:
the nucleotide sequence of SEQ ID NO: 4; or
a nucleotide sequence that is at least 95% homologous to the nucleotide sequence of SEQ ID NO: 4.
21. The pharmaceutical composition according to claim 17 wherein the nucleic acid molecule comprising a nucleotide sequence encoding the p35 subunit of IL-12, the p40 subunit of IL-12, or both is an expression vector.
22. The pharmaceutical composition according to claim 21 wherein the expression vector comprising the nucleic acid molecule encoding the p35 subunit of IL-12, the p40 subunit of IL-12, or both is the same expression vector or a different expression vector than the expression vector comprising the nucleic acid molecule encoding the HPV antigen.
23. The pharmaceutical composition according to claim 8 wherein the pharmaceutically acceptable excipient comprises a buffer.
24. The pharmaceutical composition of claim 23 , wherein the buffer is a saline-sodium citrate buffer, and wherein the composition comprises 6 mg of the vector encoding the HPV antigen per milliliter of buffer and 0.25 mg of the vector encoding the p35 subunit of IL-12, the p40 subunit of IL-1, or both, per milliliter of buffer.
25. The pharmaceutical composition of claim 24 , wherein the composition comprises 6 mg of pGX3024 per milliliter of buffer and 0.25 mg of pGX6010 per milliliter of buffer.
26. A method of inducing an immune response in a subject comprising administering to the subject an effective amount of the pharmaceutical composition according to claim 22 , to thereby induce the immune response.
27. A method of prophylactically or therapeutically immunizing a subject against HPV6 and/or HPV11 comprising administering to the subject an effective amount of the pharmaceutical composition according to claim 22 to thereby induce an immune response against HPV6, HPV11, or both.
28. A method for treating or preventing recurrent respiratory papillomatosis (RRP) in a subject comprising administering to the subject an effective amount the pharmaceutical composition according to according to claim 22 to thereby treat or prevent RRP.
29. The method according to claim 28 wherein the RRP is juvenile-onset RRP or adult-onset RRP.
30. The method according to claim 26 , wherein the administering comprises intradermal or intramuscular injection.
31. The method according to claim 30 , wherein the administering further comprises electroporation.
32. The method according to claim 27 , wherein the administering comprises intradermal or intramuscular injection.
33. The method according to claim 32 , wherein the administering further comprises electroporation.
34. The method according to claim 28 , wherein the administering comprises intradermal or intramuscular injection.
35. The method according to claim 34 , wherein the administering further comprises electroporation.