HPV vaccine
The present disclosure provides, among other things, a pharmaceutical composition that includes a lipid nanoparticle adjuvant and an anti-human papillomavirus (HPV) comprising HPV virus-like particles (VLPs) of at least one type of human papillomavirus (HPV) selected from the group consisting of HPV types: 6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 55, 56, 58, 59, 66, 68, 73, and 82.
1. A pharmaceutical composition comprising:
virus-like particles (VLPs) of at least one type of human papillomavirus (HPV) selected from the group consisting of HPV types: 6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 55, 56, 58, 59, 66, 68, 73, and 82,
a lipid nanoparticle (LNP) adjuvant, and
a pharmaceutically acceptable carrier,
wherein the LNP adjuvant comprises 30-65 mole % cationic lipid, 5-30 mole % phospholipid, 10-40 mole % cholesterol, and 0.5-4 mole % PEG-lipid.
2. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises VLPs of at least HPV types 16 and 18.
3. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises VLPs of at least HPV types 6, 11, 16, and 18.
4. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises VLPs of at least HPV types 31, 45, 52, and 58.
5. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises VLPs of at least HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.
6. The pharmaceutical composition of claim 1 , wherein the LNP adjuvant comprises 55-65 mole % cationic lipid, 5-15 mole % phospholipid, 25-35 mole % cholesterol, and 1-2.5 mole % PEG-lipid.
7. The pharmaceutical composition of claim 6 , wherein the phospholipid is DSPC, the PEG-lipid is ePEG2000-DMG, and the cationic lipid is (13Z, 16Z)—N, N-dimethyl-3-nonyldocosa 13, 16-dien-1-amine.
8. The pharmaceutical composition of claim 1 , further comprising an aluminum adjuvant.
9. A pharmaceutical composition comprising:
(a) virus like particles (VLPs) of at least one type of human papillomavirus (HPV), wherein the at least one type of HPV is selected from the group consisting of HPV types: 6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 55, 56, 58, 59, 66, 68, 73, and 82;
(b) about 100 μg to about 900 μg of an aluminum adjuvant; and
(c) about 10 μg to about 200 mg of a lipid nanoparticle (LNP) adjuvant, wherein the LNP adjuvant comprises 30-65 mole % cationic lipid, 5-30 mole % phospholipid, 10-40 mole % cholesterol, and 0.5-4 mole % PEG-lipid,
wherein each of the HPV VLPs comprise recombinant L1 or recombinant L1+L2 protein;
wherein each of the HPV VLPs are present in a concentration of about 10 μg to about 100 μg per 0.5 mL of the pharmaceutical composition;
wherein the total HPV VLP concentration is between 10 μg and 2000 μg per 0.5 mL of the pharmaceutical composition; and
wherein the HPV VLPs are adsorbed onto the aluminum adjuvant.
10. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition comprises HPV VLPs of at least HPV types 16 and 18.
11. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition comprises HPV VLPs of at least HPV types 6, 11, 16, and 18.
12. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition comprises HPV VLPs of at least HPV types 31, 45, 52, and 58.
13. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition comprises HPV VLPs of at least HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.
14. The pharmaceutical composition of claim 9 , wherein the phospholipid is DSPC, the PEG lipid is ePEG2000-DMG, and the cationic lipid is (13Z, 16Z)—N, N-dimethyl-3-nonyldocosa 13, 16-dien-1-amine.
15. The pharmaceutical composition of claim 14 , wherein the LNP adjuvant comprises 5-15 mole % DSPC, 25-35 mole % cholesterol, 1-2.5 mole % ePEG2000-DMG, and 55-65 mole % (13Z, 16Z)—N, N-dimethyl-3-nonyldocosa 13, 16-dien-1-amine.
16. The pharmaceutical composition of claim 1 , wherein the HPV VLPs comprise HPV L1 protein and do not comprise HPV L2 protein.
17. The pharmaceutical composition of claim 1 , wherein the HPV VLPs consist of HPV L1 protein.
18. A single-dose vaccine composition comprising:
a lipid nanoparticle (LNP) adjuvant, wherein the adjuvant comprises 30-65 mole % cationic lipid, 5-30 mole % phospholipid, 10-40 mole % cholesterol, and 0.5-4 mole % PEG-lipid,
virus-like particles (VLPs) of at least one type of human papillomavirus (HPV) selected from the group consisting of HPV types: 6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 55, 56, 58, 59, 66, 68, 73, and 82,
wherein the single-dose vaccine composition provides an elevated or comparable anti-HPV immune response relative to multiple doses of the same composition formulated without an LNP adjuvant.
19. The pharmaceutical composition of claim 5 , wherein the LNP adjuvant comprises 55-65 mole % cationic lipid, 5-15 mole % phospholipid, 25-35 mole % cholesterol, and 1-2.5 mole % PEG-lipid.
20. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises VLPs of at least HPV types 6, 11, 16, 18, 31, 33, 35, 45, 52, 58, and 59.
21. The pharmaceutical composition of claim 20 , wherein the LNP adjuvant comprises 55-65 mole % cationic lipid, 5-15 mole % phospholipid, 25-35 mole % cholesterol, and 1-2.5 mole % PEG-lipid.
22. A method of inducing an immune response to a human papillomavirus (HPV) in a human patient comprising administering to the patient the pharmaceutical composition of claim 1 .
23. A method of preventing infection of a human patient by a human papillomavirus (HPV) comprising administering to the patient the pharmaceutical composition of claim 1 .
24. A method of delivering a pharmaceutical composition that induces a neutralizing titer against an HPV antigen in a host comprising:
(a) administering a pharmaceutical composition to the host comprising:
a lipid nanoparticle (LNP) adjuvant, wherein the LNP adjuvant comprises 30-65 mole % cationic lipid, 5-30 mole % phospholipid, 10-40 mole % cholesterol, and 0.5-4 mole % PEG-lipid, and
virus-like particles (VLPs) of at least one type of human papillomavirus (HPV) selected from the group consisting of HPV types: 6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 55, 56, 58, 59, 66, 68, 73, and 82,
and
(b) inducing a neutralizing titer against the HPV antigen in the host,
where a single dose of the pharmaceutical composition provides enhanced or comparable neutralizing titers when compared to multiple doses of the same pharmaceutical composition when the anti-HPV composition is formulated without an adjuvant.