Therapeutic HPV16 vaccines
Provided is designer nucleic acid constructs and polypeptides that can be used as therapeutic vaccines against HPV16.
1. A recombinant pox virus vector comprising a nucleic acid sequence encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:1, wherein the nucleic acid sequence is operably linked to a promoter.
2. The recombinant pox virus vector of claim 1 , wherein the pox virus vector is a Modified Vaccinia Ankara (MVA) vector.
3. The recombinant MVA vector of claim 2 , wherein the encoded polypeptide further comprises at least one epitope of a human papillomavirus (HPV) E2 protein.
4. The recombinant MVA vector of claim 3 , wherein the encoded polypeptide comprises a HPV16 E2 protein that has a deletion or mutation in its DNA binding domain.
5. The recombinant MVA vector of claim 4 , wherein the encoded polypeptide comprises the amino acid sequence of SEQ ID NO:3 or SEQ ID NO:5.
6. The recombinant pox virus vector of claim 1 , wherein the encoded polypeptide further comprises at least one epitope of a human papillomavirus (HPV) E2 protein.
7. The recombinant pox virus vector of claim 6 , wherein the encoded polypeptide comprises a HPV16 E2 protein that has a deletion or mutation in its DNA binding domain.
8. A recombinant cell comprising the recombinant pox virus vector of claim 1 .
9. A recombinant cell comprising the recombinant MVA vector of claim 2 .
10. A method for producing a recombinant pox virus vector, comprising growing the recombinant cell of claim 8 under conditions for production of the recombinant pox virus vector.
11. A vaccine composition comprising the recombinant pox virus vector of claim 1 .
12. A vaccine composition comprising the recombinant MVA vector of claim 2 .
13. A vaccine composition comprising the recombinant MVA vector of claim 3 .
14. A method of generating an immune response against HPV16, comprising administering to a subject in need thereof the vaccine composition of claim 11 .
15. The method of claim 14 , further comprising administering to the subject a second vaccine composition comprising a recombinant adenoviral vector encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:1, wherein one of the vaccine composition of claim 11 and the second vaccine composition is administered to the subject for priming vaccination and the other is for boosting administration.
16. A method of generating an immune response against HPV16, comprising administering to a subject in need thereof the vaccine composition of claim 12 .
17. The method of claim 16 , further comprising administering to the subject a second vaccine composition comprising a recombinant human adenovirus serotype 26 (Ad26) vector encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:1, wherein one of the vaccine composition of claim 12 and the second vaccine composition is administered to the subject for priming vaccination and the other is for boosting administration.
18. A method of generating an immune response against HPV16, comprising administering to a subject in need thereof the vaccine composition of claim 13 .
19. The method of claim 18 , further comprising administering to the subject a second vaccine composition comprising a recombinant human adenovirus serotype 26 (Ad26) vector encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:1, wherein one of the vaccine composition of claim 13 and the second vaccine composition is administered to the subject for priming vaccination and the other is for boosting administration.
20. A method for treating a subject having persistent HPV infection, vulvar intraepithelial neoplasia (VIN), cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia (VaIN), anal intraepithelial neoplasia (AIN), cervical cancer, oropharyngeal cancer, penile cancer, vaginal cancer or anal cancer, the method comprising administering to the subject the vaccine composition according to claim 11 .
21. The method of claim 20 , further comprising administering to the subject a second vaccine composition comprising a recombinant adenoviral vector encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:1, wherein one of the vaccine composition of claim 11 and the second vaccine composition is administered to the subject for priming vaccination and the other is for boosting administration.
22. The method of claim 21 , wherein the method is for treating a subject having persistent HPV infection.
23. A method for treating a subject having persistent HPV infection, vulvar intraepithelial neoplasia (VIN), cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia (VaIN), anal intraepithelial neoplasia (AIN), cervical cancer, oropharyngeal cancer, penile cancer, vaginal cancer or anal cancer, the method comprising administering to the subject the vaccine composition according to claim 12 .
24. The method of claim 23 , further comprising administering to the subject a second vaccine composition comprising a recombinant human adenovirus serotype 26 (Ad26) vector encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:1, wherein one of the vaccine composition of claim 12 and the second vaccine composition is administered to the subject for priming vaccination and the other is for boosting administration.
25. The method of claim 24 , wherein the method is for treating a subject having persistent HPV infection.
26. A method for treating a subject having persistent HPV infection, vulvar intraepithelial neoplasia (VIN), cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia (VaIN), anal intraepithelial neoplasia (AIN), cervical cancer, oropharyngeal cancer, penile cancer, vaginal cancer or anal cancer, the method comprising administering to the subject the vaccine composition according to claim 13 .
27. The method of claim 26 , further comprising administering to the subject a second vaccine composition comprising a recombinant human adenovirus serotype 26 (Ad26) vector encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:1 and at least one epitope of a human papillomavirus (HPV) E2 protein, wherein one of the vaccine composition of claim 13 and the second vaccine composition is administered to the subject for priming vaccination and the other is for boosting administration.
28. The method of claim 27 , wherein the method is for treating a subject having persistent HPV infection.