Immunomodulation by iscoms, immune stimulating complexes

The iscom is a uniform stable complex consisting of cholesterol, phospholip id, adjuvant-active saponin, and antigen. The iscom matrix is a particulate complex with identical composition, shape, and morphology but lacking the incorporated antigen. The assembly of the complex is based on hydrophobic i nteractions, but antigens that are not hydrophobic can be conjugated with a hydrophobic tail or hidden hydrophobic regions can be exposed, e.g., by ac id treatment, to facilitate the incorporation into iscoms. The functional a spects of iscoms are described emphasizing immunomodulation in mouse models . Iscoms prominently enhance the antigen targeting uptake, and activity of antigen presenting cells including dendritic and B cells and macrophages re sulting in the production of proinflammatory cytokines, above all interleuk in (IL)-1, IL-6, and IL-12. The expression of costimulatory molecules major histocompatibility complex (MHC) class II, B7.1. and B7.2, is also enhance d. The latter partly explains why the iscom is an efficient adjuvant for el derly mice. Iscoms enhance the Th1 type of response with increased producti on of IL-2 and interferon g. However, with some antigens and particularly i n monkeys immunized with HIV iscoms, the production of IL-4 was enhanced. I L-4, IL-2, and interferon g (IFNg) together with the b chemokines MIP-1a an d MIP-1b correlated with protection against challenge infection with a chim eric virus (simian immunodeficiency virus-human immunodeficiency virus). Is coms were also shown to induce a potent immune response in the newborn and to be an efficient delivery system for mucosal administration. Technical in formation is given about formulation of iscoms and about handling of antige ns to optimize their incorporation into iscoms. (C) 1999 Academic Press.