Combined human papillomavirus VLP/gene delivery system and use thereof as a vaccine for prophylaxis and immunotherapy of infectious diseases and tumors
The present invention relates to compositions that contain a chimeric papillomavirus virus-like particle (VLP) in combination with a DNA molecule encoding a protein or polypeptide epitope. The chimeric papillomavirus VLP is assembled from an L1 protein or polypeptide and a chimeric protein or polypeptide containing at least a portion of the L2 protein and a protein or polypeptide including an immunogenic epitope. The composition is useful for inducing an enhanced immune response against a pathogen or a tumor.
1. A method of inducing an immune response against a pathogen comprising:
first administering to a patient an effective amount of a virus-like particle (“VLP”) comprising a papillomavirus L1 protein or polypeptide and a chimeric protein or polypeptide, the chimeric protein or polypeptide comprising a papillomavirus L2 polypeptide and a protein or polypeptide fragment comprising a first pathogen-specific epitope, which VLP is devoid of DNA; and
second administering to the patient a DNA molecule encoding a protein or polypeptide comprising the pathogen-specific epitope, wherein delivery of the DNA molecule is not dependent on VLP-mediated uptake;
wherein said first and second administering are carried out at about the same time and are effective to induce a synergistic immune response against the pathogen, as compared to the first and second administering alone.
2. The method according to claim 1 wherein the L2 polypeptide is a full-length L2 protein.
3. The method according to claim 1 wherein the L2 polypeptide is an N-terminal fragment of L2 protein.
4. The method according to claim 1 wherein the pathogen is a bacterium, a virus, a fungus, or a protozoan.
5. The method according to claim 1 wherein the DNA molecule is present in a plasmid or expression vector.
6. The method according to claim 1 wherein the VLP is a chimeric HPV-16 L1/L2-Nef fusion VLP and the DNA molecule encodes a polypeptide comprising an HIV Nef epitope.
7. The method according to claim 1 wherein the VLP is a chimeric HPV-16 L1/L2-HPV-E6 fusion VLP and the DNA molecule encodes a polypeptide comprising an HPV16 E6 epitope.
8. The method according to claim 1 wherein said first and second administering are carried out at anatomically distinct sites.
9. The method according to claim 1 further comprising repeating either said first administering or said second administering or both.
10. A method of inducing an immune response against a pathogen comprising:
administering to a patient an effective amount of a papillomavirus virus-like particle (“VLP”) comprising an L1 protein or polypeptide and a chimeric protein or polypeptide, the chimeric protein or polypeptide comprising an L2 polypeptide and a protein or polypeptide fragment comprising a pathogen-specific epitope; and
separately administering to the patient a DNA molecule encoding the protein or polypeptide comprising the pathogen-specific epitope;
wherein said administering the VLP and said separately administering the DNA molecule are carried out at about the same time and are effective to induce a synergistic immune response against the pathogen as compared to the additive effects of said administering the VLP and said separately administering the DNA molecule alone.
11. The method according to claim 10 wherein the L2 polypeptide is a full-length L2 protein.
12. The method according to claim 10 wherein the L2 polypeptide is a truncated L2 protein.
13. The method according to claim 10 wherein the L2 polypeptide is an N-terminal fragment of L2 protein.
14. The method according to claim 10 wherein the pathogen is a bacterium, a virus, a fungus, or a protozoan.
15. The method according to claim 10 wherein the VLP is a chimeric HPV-16 L1/L2-Nef fusion VLP and the pathogen-specific epitope is an HIV Nef epitope.
16. The method according to claim 10 wherein the VLP is a chimeric HPV-16 L1/L2-HPV-E6 fusion VLP and the pathogen-specific epitope is an HPV E6 epitope.
17. The method according to claim 10 further comprising repeating one or both of said administering the VLP or said separately administering the DNA molecule.
18. The method according to claim 10 wherein the DNA molecule is present in a plasmid or expression vector.
19. The method according to claim 10 wherein said administering the VLP and said separately administering the DNA molecule are carried out at anatomically distinct sites.