Saponin-antigen conjugates and the use thereof

A vaccine which comprises a saponin/antigen covalent conjugate composition or a saponin alkaline hydrolysis product/antigen covalent conjugate composition and a pharmaceutically acceptable carrier, wherein said conjugate comprises a substantially pure saponin selected from the group consisting of QA-21-V1 and QA-21-V2, or an alkaline hydrolysis product of a substantially pure saponin selected from the group consisting of QA-21-V1 and QA-21-V2, wherein said saponin or saponin alkaline hydrolysis product comprises a glucuronate carboxyl group, said saponin or said saponin alkaline hydrolysis product being linked at the glucuronate carboxyl group to an antigen either directly or through a linker group, wherein the linkage does not interfere with the ability of said substantially pure saponin or said alkaline hydrolysis product to stimulate an immune response in an animal.

A method of enhancing an immune response to an antigen in an individual comprising administration of an effective amount of a saponin/antigen covalent conjugate composition or a saponin alkaline hydrolysis product/antigen covalent conjugate composition and a pharmaceutically acceptable carrier, wherein said conjugate comprises a substantially pure saponin selected from the group consisting of QA-21-V1 and QA-21-V2, or an alkaline hydrolysis product of a substantially pure saponin selected from the group consisting of QA-21-V1 and QA-21-V2, wherein said saponin or saponin alkaline hydrolysis product comprises a glucuronate carboxyl group, said saponin or said saponin alkaline hydrolysis product being linked at the glucuronate carboxyl group to an antigen either directly or through a linker group, wherein the linkage does not interfere with the ability of said substantially pure saponin or said alkaline hydrolysis product to stimulate an immune response in an animal.

Substantially pure QA-21-V 1 saponin, wherein said pure saponin is characterized by a peak at 6.4 minutes on HILIC on a PolyLC PHEA column having 5 .mu.m particle size, 4.6 mm ID.times.200 mm L in a solvent of 10 mM TEAP, pH 6.0, in water/acetonitrile (15/85 %, v/v) at a flow rate of 1 ml/min.

Substantially pure QA-21-V2 saponin, wherein said pure saponin is characterized by a peak at 6.9 minutes on HILIC on a PolyLC PHEA column having 5 .mu.m particle size, 4.6 mm ID.times.200 mm L in a solvent of 10 mM TEAP, pH 6.0, in water/acetonitrile (15/85 %, v/v) at a flow rate of 1 ml/min.

Substantially pure modified saponin QA-7 which is reduced to an alcohol group at the triterpine aldehyde.