Vaccines for human papilloma virus and methods for using the same
Improved anti-HPV immunogens and nucleic acid molecules that encode them are disclosed. Immunogens disclosed include those having consensus HPV6 E6E7, HPV11 E6E7, HPV16 E6E7, HPV18 E6E7, HPV31 E6E7, HPV33 E6E7, HPV39 E6E7, HPV45 E6E7, HPV52 E6E7, and HPV58 E6E7. Pharmaceutical composition, recombinant vaccines comprising DNA plasmid and live attenuated vaccines are disclosed as well methods of inducing an immune response in an individual against HPV are disclosed.
1. A composition comprising at least one nucleotide sequence encoding at least one HPV E6-E7 fusion antigen from at least one HPV subtype, wherein the at least one HPV subtype comprises HPV31; wherein the nucleotide sequence encoding the HPV31 E6-E7 fusion antigen encodes an amino acid sequence that is at least 98% homologous to SEQ ID NO:18.
2. The composition of claim 1 , further comprising at least one nucleotide sequence encoding at least one HPV E6-E7 fusion antigen selected from the group consisting of:
nucleotide sequence that encodes SEQ ID NO:2; nucleotide sequence that encodes SEQ ID NO:4; nucleotide sequence that encodes SEQ ID NO:6; nucleotide sequence that encodes SEQ ID NO:8; nucleotide sequence that encodes SEQ ID NO:20; nucleotide sequence that encodes SEQ ID NO:22; nucleotide sequence that encodes SEQ ID NO:24;
a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence nucleotide sequence that encodes SEQ ID NO:2; a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:4; a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:6; a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:8; a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:20; a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:22; and a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:24.
3. The composition of claim 1 , comprising one or more nucleotide sequences encoding an HPV E6-E7 fusion antigen selected from the group consisting of:
SEQ ID NO:1; SEQ ID NO:3; SEQ ID NO:5; SEQ ID NO:7; SEQ ID NO: 17; SEQ ID NO:19; SEQ ID NO:21; SEQ ID NO:23;
a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:1; a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:3; a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:5; a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:7; a nucleic acid sequence that is at least 95% homologous to SEQ ID NO: 17; a nucleic acid sequence that is at least 95% homologous to SEQ ID NO: 19; a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:21; and a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:23.
4. The composition of claim 2 , wherein at least one nucleotide sequence encoding at least one HPV E6-E7 fusion antigen is selected from the group consisting of:
nucleotide sequence that encodes SEQ ID NO:2; nucleotide sequence that encodes SEQ ID NO:4; nucleotide sequence that encodes SEQ ID NO:6; nucleotide sequence that encodes SEQ ID NO:8; nucleotide sequence that encodes SEQ ID NO:20; nucleotide sequence that encodes SEQ ID NO:22; nucleotide sequence that encodes SEQ ID NO:24;
a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence nucleotide sequence that encodes SEQ ID NO:2; a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:4; a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:6; a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:8; a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:20; a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:22; and a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:24.
5. The composition of claim 2 , wherein at least one nucleotide sequence encoding at least one HPV E6-E7 fusion antigen is selected from the group consisting of:
nucleotide sequence that encodes SEQ ID NO:6; nucleotide sequence that encodes SEQ ID NO:8; nucleotide sequence that encodes SEQ ID NO:20; nucleotide sequence that encodes SEQ ID NO:22; nucleotide sequence that encodes SEQ ID NO:24;
a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:6; a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:8; a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:20; a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:22; and a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:24.
6. The composition of claim 2 , wherein one or more nucleotide sequences encoding the HPV E6-E7 fusion antigen is selected from the group consisting of:
nucleotide sequence that encodes SEQ ID NO:2; nucleotide sequence that encodes SEQ ID NO:4; nucleotide sequence that encodes SEQ ID NO:22; nucleotide sequence that encodes SEQ ID NO:24; and
a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence that encodes SEQ ID NO:2; a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence that encodes SEQ ID NO:4; a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence that encodes SEQ ID NO:22; and a nucleic acid sequence that is at least 95% homologous to a nucleic acid sequence that encodes SEQ ID NO:24.
7. The composition of claim 2 , wherein at least one nucleotide sequence encoding at least one HPV E6-E7 fusion antigen is selected from the group consisting of:
nucleotide sequence that encodes SEQ ID NO:20; nucleotide sequence that encodes SEQ ID NO:22;
a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:20; and a nucleic acid sequence that is at least 95% homologous to a nucleotide sequence that encodes SEQ ID NO:22.
8. The composition of claim 2 , wherein at least one nucleotide sequence encoding at least one HPV E6-E7 fusion antigen has at least 98% homology with at least one nucleotide sequence selected from the group consisting of:
nucleotide sequence that encodes SEQ ID NO:2; nucleotide sequence that encodes SEQ ID NO:4; nucleotide sequence that encodes SEQ ID NO:6; nucleotide sequence that encodes SEQ ID NO:8; nucleotide sequence that encodes SEQ ID NO:20; nucleotide sequence that encodes SEQ ID NO:22; and nucleotide sequence that encodes SEQ ID NO:24.
9. The composition of claim 2 , wherein at least one nucleotide sequence encoding at least one HPV E6-E7 fusion antigen has at least 99% homology with at least one nucleotide sequence selected from the group consisting of:
nucleotide sequence that encodes SEQ ID NO:2; nucleotide sequence that encodes SEQ ID NO:4; nucleotide sequence that encodes SEQ ID NO:6; nucleotide sequence that encodes SEQ ID NO:8; nucleotide sequence that encodes SEQ ID NO:20; nucleotide sequence that encodes SEQ ID NO:22; and nucleotide sequence that encodes SEQ ID NO:24.
10. The composition of claim 2 , where the nucleotide sequences encoding the HPV E6-E7 fusion antigen are without a leader sequence at 5′ end that is a nucleotide sequence that encodes SEQ ID NO:10.
11. The composition of claim 3 , comprising one or more nucleotide sequences encoding an HPV E6-E7 fusion antigen selected from the group consisting of:
SEQ ID NO:5; SEQ ID NO:7; SEQ ID NO:17; SEQ ID NO:19; SEQ ID NO:21; SEQ ID NO:23;
a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:5; a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:7; a nucleic acid sequence that is at least 95% homologous to SEQ ID NO: 17; a nucleic acid sequence that is at least 95% homologous to SEQ ID NO: 19; a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:21; and a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:23.
12. The composition of claim 7 , comprising one or more nucleotide sequences encoding an HPV E6-E7 fusion antigen selected from the group consisting of:
SEQ ID NO:1; SEQ ID NO:3; SEQ ID NO:21; SEQ ID NO:23;
a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:1; a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:3; a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:21; and a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:23.
13. The composition of claim 3 , comprising one or more nucleotide sequences encoding an HPV E6-E7 fusion antigen selected from the group consisting of:
SEQ ID NO:17; SEQ ID NO:19; SEQ ID NO:21;
a nucleic acid sequence that is at least 95% homologous to SEQ ID NO: 17; a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:19; and a nucleic acid sequence that is at least 95% homologous to SEQ ID NO:21.
14. The composition of claim 3 , wherein one or more nucleotide sequences encoding the HPV E6-E7 fusion antigen has at least 98% homology with nucleotide sequences selected from the group consisting of: SEQ ID NO:1; SEQ ID NO:3; SEQ ID NO:5; SEQ ID NO:7; SEQ ID NO:17; SEQ ID NO:19; SEQ ID NO:21; and SEQ ID NO: 23.
15. The composition of claim 3 , wherein one or more nucleotide sequences encoding the HPV E6-E7 fusion antigen has at least 99% homology with nucleotide sequences selected from the group consisting of: SEQ ID NO:1; SEQ ID NO:3; SEQ ID NO:5; SEQ ID NO:7; SEQ ID NO:17; SEQ ID NO:19; SEQ ID NO:21; and SEQ ID NO: 23.
16. The composition of claim 7 , where the nucleotide sequences encoding the HPV E6-E7 fusion antigen are without a leader sequence at 5′ end that has nucleotide sequence SEQ ID NO:9.
17. The composition of claim 2 , wherein said nucleotide sequence is a plasmid.
18. A pharmaceutical composition comprising a nucleotide sequence of claim 2 .
19. A method of inducing an effective immune response in an individual against more than one subtype of HPV, comprising administering to said individual a composition comprising a nucleotide sequence of claim 2 .
20. The method of claim 19 , wherein said nucleotide sequence is administered into the individual by electroporation.
21. A method of inducing an effective immune response in an individual against more than one subtype of HPV, comprising administering to said individual a composition comprising a nucleotide sequence of claim 3 .
22. The method of claim 21 , wherein said nucleotide sequence is administered into the individual by electroporation.