ISCOM preparation and use thereof
The invention relates to a composition comprising a mixture of at least two iscom complexes each complex comprising essentially one saponin fraction from Quillaja Saponaria Molina. The complexes may be iscom complexes or iscom matrix complexes. The invention also pertains to the use of such a mixture for the preparation of an immunomodulating pharmaceutical, and adjuvant, formulations for immunization, e.g. for production of monoclonal antibodies, and a vaccine. Kits of parts comprising at least two parts, wherein each part comprises one iscom complex or one iscom matrix complex according to the invention are also embraced.
1. A composition comprising at least two iscom particles, wherein:
the first iscom particle comprises fraction A of Quillaja saponaria Molina and not fraction C of Quillaja saponaria Molina; and
the second iscom particle comprises fraction C of Quillaja saponaria Molina and not fraction A of Quillaja saponaria Molina.
2. The composition of claim 1 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 50% to 70% by weight and 50% to 30% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
3. The composition of claim 1 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 30% to 50% by weight and 70% to 50% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
4. The composition of claim 1 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 75% to 99.5% by weight and 25% to 0.5% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
5. The composition of claim 1 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 90% to 99% by weight and 10% to 1% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
6. The composition of claim 1 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 91% to 98% by weight and 9% to 2% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
7. The composition of claim 1 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 92% to 96% by weight and 8% to 4% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
8. The composition of claim 1 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 0.1% to 99.9% by weight and 99.9% to 0.1% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
9. The composition of claim 1 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 5% to 95% by weight and 95% to 5% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
10. The composition of claim 1 , wherein the first iscom particle is selected from the group consisting of iscom matrix complex particle and iscom complex particle.
11. The composition of claim 1 , wherein the second iscom particle is selected from the group consisting of iscom matrix complex particle and iscom complex particle.
12. The composition of claim 1 , wherein the composition has a lower toxicity than a corresponding composition in which corresponding amounts of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina are integrated together in iscom particles of the corresponding composition instead of separately in the first and second iscom particles.
13. A composition comprising at least two iscom particles, wherein: the first iscom particle consists essentially of fraction A of Quillaja saponaria Molina; the second iscom particle consists essentially of fraction C of Quillaja saponaria Molina; and the composition has a lower toxicity than a corresponding composition in which corresponding amounts of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina are integrated together in iscom particles of the corresponding composition instead of separately in the first and second iscom particles.
14. The composition of claim 13 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 50% to 70% by weight and 50% to 30% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
15. The composition of claim 13 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 30% to 50% by weight and 70% to 50% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
16. The composition of claim 13 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 75% to 99.5% by weight and 25% to 0.5% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
17. The composition of claim 13 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 90% to 99% by weight and 10% to 1% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
18. The composition of claim 13 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 91% to 98% by weight and 9% to 2% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
19. The composition of claim 13 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 92% to 96% by weight and 8% to 4% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
20. The composition of claim 13 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 0.1% to 99.9% by weight and 99.9% to 0.1% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
21. The composition of claim 13 , wherein fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina account for 5% to 95% by weight and 95% to 5% by weight, respectively, of the sum of weights of fraction A of Quillaja saponaria Molina and fraction C of Quillaja saponaria Molina in the composition.
22. The composition of claim 13 , wherein the first iscom particle is selected from the group consisting of iscom matrix complex particle and iscom complex particle.
23. The composition of claim 13 , wherein the second iscom particle is selected from the group consisting of iscom matrix complex particle and iscom complex particle.
24. A method of immunization comprising administering the composition of claim 1 to a human or an animal.
25. The method of claim 24 , wherein:
the composition has a lower toxicity than a corresponding composition in which corresponding amounts of fraction A of Quillaja saponaria Molina and fraction C of Quillaja Saponaria Molina are integrated together in iscom particles of the corresponding composition instead of separately in the first and second iscom particles; and
the administration enhances cell-mediated and antibody responses in the human or the animal in comparison to administering the corresponding composition.
26. A method of immunization comprising administering the composition of claim 13 to a human or an animal.