On the structure of immune-stimulating saponin-lipid complexes (iscoms)

Immune-stimulating complexes (iscoms) are stable complexes of cholesterol, phospholipid and Quil A, a triterpene saponin mixture in the size range from 40 to 100 nm. They can be used as antigen carriers in subunit vaccines. In this paper it is demonstrated that iscoms are rigid, negatively charged vesicles in which small water soluble molecules like carboxyfluorescein cannot be retained. The negative zeta-potential prevents iscoms from aggregation. The chemical composition of iscoms in one dispersion varied considerably. A typical example of the composition of iscoms is cholesterol/phospholipid/Quil A = 1.0:1.2:6.2 by weight for the iscom matrix, that is iscoms without antigen, and 1.0:1.3:5.1 for antigen-containing iscoms. A hypothetical model for the structure of the iscom matrix and related structures is presented, based on analytical chemical, physico-chemical and electronmicroscopic data. In this model iscoms are considered to be multi-micellar structures, shaped and stabilized by hydrophobic interactions, electrostatic repulsion, steric factors and possibly hydrogen bonds. The individual micelles are relatively flat, ring-shaped structures, the center offering space for one of the two bulky sugar chains of the saponins.