Quil A fraction with low toxicity and use thereof
Fraction A of Quil A can be used together with at least one other adjuvant for the preparation of an adjuvant composition, where the included adjuvant components act synergistically to enhance level of immune response and have synergistic immunomodulating activity on the co-administered antigens or immunogens. Other adjuvants can comprise saponins, naturally occurring, synthetic or semisynthetic saponin molecules; e.g. saponins and saponin fractions from Quil A, cell wall skeleton, blockpolymers, TDM, lipopeptides, LPS and LPS-derivatives, Lipid A from different bacterial species and derivatives thereof, e.g., monophosphoryl lipid A. CpG variants, CT and LT or fractions thereof.
1. A method of enhancement of an immune response level and an immunomodulating activity comprising intraperitoneally or subcutaneously administering to a subject an effective amount of an adjuvant composition with synergistic effect of low toxicity comprising
(i) immunostimulating complex (ISCOM) particles comprising a saponin fraction consisting essentially of fraction A of Quil A, and
(ii) at least one other adjuvant,
wherein the ISCOM particles comprising the saponin fraction consisting essentially of fraction A of Quil A are less toxic on VERO cells than are QH703 ISCOM matrix particles, and
the at least one other adjuvant is in free form or integrated into ISCOM particles other than the ISCOM particles comprising the saponin fraction consisting essentially of fraction A of Quil A.
2. The method according to claim 1 wherein said at least one other adjuvant is chosen from the group consisting of: saponins, naturally occurring saponin molecules derived from crude saponin extract of Quillaja saponaria Molina, synthetic saponin molecules derived from crude saponin extract of Quillaja saponaria Molina, semisynthetic saponin molecules derived from crude saponin extract of Quillaja saponaria Molina, a saponin fraction of Quil A, saponin fractions from cell wall skeleton, blockpolymers, hydrophilic block copolymers, CRL-1005, Threhalose di mucolate (TDM), lipopeptides, LPS and LPS-derivatives, Lipid A from a bacterial species and derivatives thereof, monophosphoryl lipid A, CpG variants, CpGODN variants, endogenous human animal immunomodulators, GM-CSF, IL-2, native adjuvant active bacterial toxins, modified adjuvant active bacterial toxins, cholera toxin CT, CT subcomponent CTB, CT subcomponent CTAT, thermolabile toxin (LT) of E. coli, Bordetella pertussis (BP) toxin, and a filamentus heamagglutenin of BP.
3. The method according to claim 2 wherein the saponin fraction of Quil A is fraction C of Quil A or fraction B of Quil A.
4. The method according to claim 1 , wherein said at least one other adjuvant is integrated into ISCOM particles other than the ISCOM particles comprising the saponin fraction consisting essentially of fraction A of Quil A.
5. The method according to claim 1 , wherein
said at least one other adjuvant is integrated into ISCOM particles other than the ISCOM particles comprising the saponin fraction consisting essentially of fraction A of Quil A and is not integrated into the ISCOM particles comprising the saponin fraction consisting essentially of fraction A of Quil A.
6. The method according to claim 1 , wherein said at least one other adjuvant is not integrated into ISCOM particles.
7. The method according to claim 6 , wherein said at least one other adjuvant is at least one of monophosphoryl lipid A and cholera toxin CT.
8. The method according to claim 1 , wherein said ISCOM particles comprising the saponin fraction consisting essentially of fraction A of Quil A are ISCOM complexes.
9. The method according to claim 1 , wherein said ISCOM particles comprising the saponin fraction consisting essentially of fraction A of Quil A are ISCOM matrix complexes.
10. The method according to claim 3 , wherein the composition comprises
50-99.9% of fraction A of Quil A; and
0.1-50% of the saponin fraction of Quil A based on the total weight of the composition.
11. The method according to claim 10 , wherein the composition comprises
75-99.9% of fraction A of Quil A; and
0.1-25% of the saponin fraction of Quil A based on the total weight of the composition.
12. The method according to claim 11 , wherein the composition comprises
91-99.1% of fraction A of Quil A; and
0.1-9% of the saponin fraction of Quil A based on the total weight of the composition.
13. The method according to claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier, diluent, excipient or additive.
14. The method according to claim 1 , wherein the immune response is an IgG response.
15. The method according to claim 1 , wherein the immune response is a Th1 response.
16. The method according to claim 1 , wherein the immune response is a Th2 response.
17. The method according to claim 1 , wherein the immunomodulating activity is a Th1-Th2 balance.