Polychlorinated biphenyls and squalene-containing adjuvants
When using squalene in a vaccine adjuvant, there is a possibility of contamination with polychlorinated biphenyls (PCBs). Environmental exposure to PCBs may adversely affect children's immune responses to routine vaccinations. Thus the invention uses squalene with low or no PCB contamination, particularly when derived from shark liver.
1. An oil-in-water emulsion adjuvant comprising squalene, wherein the emulsion comprises less than 661 picograms of polychlorinated biphenyls (PCBs) per gram of squalene (toxic equivalent; TEQ).
2. A vaccine composition comprising an antigen and an oil-in-water emulsion according to claim 1 .
3. A process for preparing an oil-in-water emulsion, comprising mixing an oil component and an aqueous component, wherein the oil component comprises squalene and has less than 661 picograms of polychlorinated biphenyls (PCBs) per gram of squalene (toxic equivalent; TEQ).
4. A process for preparing a vaccine, comprising mixing an oil component, an aqueous component and an antigen, wherein the oil component comprises squalene and has less than 661 picograms of polychlorinated biphenyls (PCBs) per gram of squalene (toxic equivalent; TEQ).
5. The process of claim 3 , wherein the oil component and aqueous component are mixed with a surfactant.
6. The process of claim 4 , wherein the oil component and aqueous component are mixed with a surfactant.
7. The process of claim 5 , wherein the process comprises microfluidising the oil component, the aqueous component and the surfactant.
8. The process of claim 6 , wherein the process comprises microfluidising the oil component, the aqueous component and the surfactant.
9. The process of claim 7 , wherein microfluidisation provides an emulsion with submicron droplets.
10. The process of claim 8 , wherein microfluidisation provides an emulsion with submicron droplets.
11. A process for preparing a vaccine, comprising: (i) preparing an emulsion by the process of claim 3 ; and (ii) packaging the emulsion into a kit as a kit component together with an antigen component.
12. The process of claim 3 , wherein the oil component comprises shark-derived squalene.
13. The process of claim 4 , wherein the oil component comprises shark-derived squalene.
14. The process of claim 3 , wherein the oil component comprises squalene from a non-shark source.
15. The process of claim 4 , wherein the oil component comprises squalene from a non-shark source.
16. The emulsion of claim 1 , wherein the emulsion comprises less than 10 picograms of PCBs per gram of squalene (TEQ).
17. The vaccine of claim 2 , wherein the emulsion comprises less than 10 picograms of PCBs per gram of squalene (TEQ).
18. An oil-in-water emulsion adjuvant comprising squalene, wherein the emulsion contains no hexachlorobiphenyl.
19. The emulsion of claim 18 , wherein the emulsion contains no 3′,4,4′,5,5′-hexachlorobiphenyl.
20. An oil-in-water emulsion adjuvant comprising squalene, wherein the emulsion contains no 3,3′,4,4′,5-pentachlorobiphenyl.
21. An oil-in-water emulsion adjuvant comprising squalene, wherein the emulsion contains no 3,3′,4,4′-tetrachlorobiphenyl.
22. An oil-in-water emulsion adjuvant comprising squalene, wherein the emulsion contains no 3,4,4′,5-tetrachlorobiphenyl.
23. The emulsion of claim 1 , wherein the TEQ is calculated based on the twelve non-ortho and mono-ortho substituted PCBs.
24. The vaccine of claim 2 , wherein the TEQ is calculated based on the twelve non-ortho and mono-ortho substituted PCBs.
25. The emulsion of claim 1 , wherein the emulsion comprises squalene and a polyoxyethylene sorbitan ester surfactant.
26. The vaccine of claim 2 , wherein the emulsion comprises squalene and a polyoxyethylene sorbitan ester surfactant.
27. The emulsion of claim 25 , wherein the polyoxyethylene sorbitan ester surfactant is polysorbate 80.
28. The vaccine of claim 26 , wherein the polyoxyethylene sorbitan ester surfactant is polysorbate 80.
29. The emulsion of claim 1 , wherein the emulsion comprises squalene and a sorbitan ester.
30. The vaccine of claim 2 , wherein the emulsion comprises squalene and a sorbitan ester.
31. The emulsion of claim 29 , wherein the sorbitan ester is sorbitan trioleate.
32. The vaccine of claim 30 , wherein the sorbitan ester is sorbitan trioleate.
33. The emulsion of claim 1 , wherein the emulsion comprises between 5-20% by volume of oil.
34. The vaccine of claim 2 , wherein the emulsion comprises between 5-20% by volume of oil.
35. The emulsion of claim 1 , wherein the emulsion comprises from 0.5-5% by volume of surfactant.
36. The vaccine of claim 2 , wherein the emulsion comprises from 0.5-5% by volume of surfactant.
37. The emulsion of claim 1 , wherein the emulsion comprises squalene, polysorbate 80, and sorbitan trioleate.
38. The vaccine of claim 2 , wherein the emulsion comprises squalene, polysorbate 80, and sorbitan trioleate.
39. The emulsion of claim 1 , wherein the emulsion comprises squalene, an α-tocopherol, and polysorbate 80.
40. The vaccine of claim 2 , wherein the emulsion comprises squalene, an α-tocopherol, and polysorbate 80.
41. A process for preparing a vaccine, comprising: (i) providing an emulsion according to claim 1 ; and (ii) packaging the emulsion into a kit as a kit component together with an antigen component.
42. A kit comprising an emulsion according to claim 1 and instructions for administration.
43. A kit comprising as separate components (i) an emulsion according to claim 1 ; and (ii) an antigen.