Inactivated dengue virus vaccine with aluminium-free adjuvant
The present disclosure provides immunogenic compositions for the prevention and/or treatment of disease caused by dengue virus.
1. An immunogenic composition comprising at least one inactivated dengue virus antigen and an adjuvant suitable for administration to a human subject, wherein the adjuvant comprises an oil in water emulsion, and the adjuvant is aluminum-free and does not contain any of the following: i) an immunostimulatory oligonucleotide, ii) QS21 and iii) 3D-MPL, wherein said oil in water emulsion comprises a metabolisable oil, a tocol and an emulsifier.
2. The immunogenic composition of claim 1 , wherein the at least one inactivated dengue virus antigen is selected from the group consisting of a Dengue-1 virus antigen, a Dengue-2 virus antigen, a Dengue-3 virus antigen and a Dengue-4 virus antigen.
3. The immunogenic composition of claim 1 , wherein the at least one inactivated dengue virus antigen comprises a Dengue-2 virus antigen.
4. The immunogenic composition of claim 1 , wherein the at least one inactivated dengue virus antigen is an inactivated whole dengue virus.
5. The immunogenic composition of claim 1 , wherein the oil in water emulsion adjuvant comprises squalene.
6. The immunogenic composition of claim 1 , wherein the tocol is alpha-tocopherol.
7. The immunogenic composition of claim 1 , wherein the oil in water emulsion adjuvant comprises a nonionic surfactant emulsifier.
8. The immunogenic composition of claim 7 , wherein the nonionic surfactant is polyoxyethylene sorbitan monooleate.
9. The immunogenic composition of claim 1 , wherein the oil in water emulsion adjuvant is formulated in a dose comprising:
from about 2% to about 10% squalence,
from about 2% to about 10% alpha-tocopherol,
from about 0.3% to about 3% polyoxyethylene sorbitan monooleate.
10. The immunogenic composition of claim 9 , wherein the oil in water emulsion adjuvant is formulated in a dose comprising:
from about 10 mg to about 12 mg squalene,
from about 10 mg to about 12 mg alpha-tocopherol,
from about 4 mg to about 6 mg polyoxyethylene sorbitan monooleate.
11. The immunogenic composition of claim 10 , wherein the oil in water emulsion adjuvant is formulated in a dose comprising:
10.68 mg squalene,
11.86 mg alpha-tocopherol,
4.85 mg polyoxyethylene sorbitan monooleate.
12. The immunogenic composition of claim 9 , wherein the oil in water emulsion adjuvant is formulated in a fractional dose comprising a fraction of the quantity of each of:
from about 10 mg to about 12 mg squalene,
from about 10 mg to about 12 mg alpha-tocopherol,
from about 4 mg to about 6 mg polyoxyethylene sorbitan monooleate,
wherein the fraction is selected from 1/2, 1/3, 1/4 and 1/6.
13. A method for producing a dengue vaccine comprising providing at least one purified inactivated dengue virus antigen; and formulating the at least one purified inactivated dengue virus antigen with an adjuvant suitable for administration to a human subject, wherein the adjuvant comprises an oil in water emulsion, and the adjuvant is aluminum-free and does not contain any one of the following: i) an immunostimulatory oligonucleotide, ii) QS21 and iii) 3D-MPL, wherein said oil in water emulsion comprises a metabolisable oil, a tocol and an emulsifier.
14. The immunogenic composition of claim 1 , wherein the at least one inactivated dengue virus antigen is a purified inactivated whole dengue virus.
15. The immunogenic composition of claim 1 wherein the immunogenic composition comprises inactivated whole Dengue-1 virus, inactivated whole Dengue-2 virus, inactivated whole Dengue-3 virus and inactivated whole Dengue-4 virus.
16. The immunogenic composition of claim 1 wherein the immunogenic composition comprises purified inactivated whole Dengue-1 virus, purified inactivated whole Dengue-2 virus, purified inactivated whole Dengue-3 virus and purified inactivated whole Dengue-4 virus.
17. The method of claim 13 , wherein the at least one purified inactivated dengue virus antigen is a whole killed virus inactivated by one or more steps of contacting or exposing a live virus to an agent selected from the group of: formaldehyde, betapropiolactone (BPL), hydrogen peroxide, ultraviolet irradiation and gamma irradiation.
18. A method for preventing, ameliorating or treating disease caused by dengue virus in a human subject comprising: administering the immunogenic composition of claim 1 to the subject.
19. The immunogenic composition of claim 2 , wherein the immunogenic composition comprises a Dengue-1 virus antigen, a Dengue-2 virus antigen, a Dengue-3 virus antigen and a Dengue-4 virus antigen.