Papillomavirus-like particles (VLP) as broad spectrum human papillomavirus (HPV) vaccines
This invention relates, e.g., to a virus-like particle (VLP) composition assembled from a chimeric polypeptide comprising a papilloma virus (e.g., human papillomavirus, or HPV) L1 major capsid protein, into which is inserted a surface-displayed peptide comprising a neutralizing epitope of a papillomavirus L2 protein. Vaccine compositions comprising the VLP are described, as well as methods for inducing an immune response (e.g., vaccinating) a subject against papilloma virus, using the VLP, and kits comprising the VLP, for carrying out a method of the invention.
1. A capsomere composition, assembled from a chimeric polypeptide comprising a papillomavirus (PV) L1 protein, into the DE loop of which is inserted a surface-displayed peptide consisting of one of the following sequences from a HPV16 L2 protein:
a) QLYKTCKQAGTCPPDIIPKV (SEQ ID NO:9), or
b) QLYKTCKQAGTCPPDIIPKVEG (SEQ ID NO: 56), or
c) LYKTCKQAGTCPPDIIPKVEG (SEQ ID NO:57).
2. A virus-like particle (VLP) composition, assembled from a chimeric polypeptide comprising a papilloma virus (PV) L1 protein into which is inserted into a DE loop of the L1 protein a surface-displayed peptide consisting of the following sequence from a papillomavirus L2 protein, wherein the inserted L2 peptide is from the HPV 16 L2 (17-36) peptide, and has the amino acid sequence QLYKTCKQAGTCPPDIIPKV (SEQ ID NO:9).
3. The VLP of claim 2 , wherein the L1 protein is from HPV16, and the L2 peptide is inserted between amino acids 136 and 137 in the DE loop of the L1 protein (SEQ ID NO:85); or the L1 protein is from BPV1, and the L2 peptide is inserted between amino acids 133 and 134 in the DE loop of the L1 protein (SEQ ID NO:83).
4. The VLP composition of claim 2 , which is an immunogenic composition.
5. The VLP composition of claim 4 , which is immunogenic against mucosal high-risk or low-risk, cutaneous low risk, and/or cutaneous beta-type papillomaviruses.
6. A vaccine, comprising a VLP composition of claim 2 and an adjuvant.
7. The vaccine of claim 6 , which is effective against human papillomaviruses.
8. The vaccine of claim 6 , wherein the composition is formulated for administration by inhalation, ingestion, or intramuscular injection.
9. A nucleic acid encoding the chimeric polypeptide of claim 2 .
10. A method for making a VLP or a capsomere composition, comprising incubating a chimeric polypeptide of claim 2 under suitable conditions for self-assembly.
11. A method for immunizing or vaccinating a subject against a PV, comprising administering to the subject an effective amount of a VLP composition of claim 2 .
12. A method for inducing an immune response against HPV in a subject, comprising administering to the subject an effective amount of a VLP composition of claim 2 .
13. A method for treating a PV infection in a subject having a PV infection or at risk of being exposed to PV, comprising administering to the subject an effective amount of a VLP composition of claim 2 .
14. A method for preventing cervical, anogenital, oropharyngeal cancer, or a precancer, in a subject, comprising administering to the subject an effective amount of a VLP composition of claim 2 .
15. A kit comprising a VLP composition of claim 2 .
16. A virus-like particle (VLP) composition, assembled from a chimeric polypeptide comprising a papilloma virus (PV) L1 protein into which is inserted into the DE loop of the L1 protein a surface-displayed peptide consisting of the following sequence from a papillomavirus L2 protein, wherein the inserted L2 peptide is from the HPV 16 L2 (17-38) peptide, and has the amino acid sequence QLYKTCKQAGTCPPDIIPKVEG (SEQ ID NO: 56).
17. The VLP of claim 16 , wherein the L1 protein is from HPV16, and the L2 peptide is inserted between amino acids 136 and 137 in the DE loop of the L1 protein (SEQ ID NO:85); or the L1 protein is from BPV1, and the L2 peptide is inserted between amino acids 133 and 134 in the DE loop of the L1 protein (SEQ ID NO:83).
18. The VLP composition of claim 16 , which is an immunogenic composition.
19. The VLP composition of claim 18 , which is immunogenic against mucosal high-risk or low-risk, cutaneous low risk, and/or cutaneous beta-type papillomaviruses.
20. A vaccine, comprising a VLP composition of claim 16 and an adjuvant.
21. The vaccine of claim 20 , which is effective against human papillomaviruses.
22. The vaccine of claim 20 , wherein the composition is formulated for administration by inhalation, ingestion, or intramuscular injection.
23. A nucleic acid encoding the chimeric polypeptide of claim 16 .
24. A method for making a VLP or a capsomere composition, comprising incubating a chimeric polypeptide of claim 16 under suitable conditions for self-assembly.
25. A method for immunizing or vaccinating a subject against a PV, comprising administering to the subject an effective amount of a VLP composition of claim 16 .
26. A method for inducing an immune response against HPV in a subject, comprising administering to the subject an effective amount of a VLP composition of claim 16 .
27. A method for treating a PV infection in a subject having a PV infection or at risk of being exposed to PV, comprising administering to the subject an effective amount of a VLP composition of claim 16 .
28. A method for preventing cervical, anogenital, oropharyngeal cancer, or a precancer, in a subject, comprising administering to the subject an effective amount of a VLP composition of claim 16 .
29. A kit comprising a VLP composition of claim 16 .
30. A virus-like particle (VLP) composition, assembled from a chimeric polypeptide comprising a papilloma virus (PV) L1 protein into which is inserted into the DE loop of the L1 protein a surface-displayed peptide consisting of the following sequence from a papillomavirus L2 (18-38) peptide, wherein the inserted L2 peptide is from the HPV 16 L2 protein, and has the amino acid sequence LYKTCKQAGTCPPDIIPKVEG (SEQ ID NO:57).
31. The VLP of claim 30 , wherein the L1 protein is from HPV16, and the L2 peptide is inserted between amino acids 136 and 137 in the DE loop of the L1 protein (SEQ ID NO:85); or the L1 protein is from BPV1, and the L2 peptide is inserted between amino acids 133 and 134 in the DE loop of the L1 protein (SEQ ID NO:83).
32. The VLP composition of claim 30 , which is an immunogenic composition.
33. The VLP composition of claim 32 , which is immunogenic against mucosal high-risk or low-risk, cutaneous low risk, and/or cutaneous beta-type papillomaviruses.
34. A vaccine, comprising a VLP composition of claim 30 and an adjuvant.
35. The vaccine of claim 34 , which is effective against human papillomaviruses.
36. The vaccine of claim 34 , wherein the composition is formulated for administration by inhalation, ingestion, or intramuscular injection.
37. A nucleic acid encoding the chimeric polypeptide of claim 30 .
38. A method for making a VLP or a capsomere composition, comprising incubating a chimeric polypeptide of claim 30 under suitable conditions for self-assembly.
39. A method for immunizing or vaccinating a subject against a PV, comprising administering to the subject an effective amount of a VLP composition of claim 30 .
40. A method for inducing an immune response against HPV in a subject, comprising administering to the subject an effective amount of a VLP composition of claim 30 .
41. A method for treating a PV infection in a subject having a PV infection or at risk of being exposed to PV, comprising administering to the subject an effective amount of a VLP composition of claim 30 .
42. A method for preventing cervical, anogenital, oropharyngeal cancer, or a precancer, in a subject, comprising administering to the subject an effective amount of a VLP composition of claim 30 .
43. A kit comprising a VLP composition of claim 30 .