ISCOMs and other saponin based adjuvants

Saponins are chemically a heterogeneous group of sterol glycosides and triterpene glycosides which are common constituents of plants. One source of triterpenoid saponins obtained from the bark of Quillaia saponaria Molina (the soap bark tree) have been known to cause substantial enhancement of immune responses since the 1920s. Despite their use in animal vaccines, the development of saponin-based formulations for human vaccines has been impeded by their complexity and concerns about toxicity. This review briefly covers the use of saponins for animal vaccines but focuses mainly on the development of these adjuvants for use in man. Important aspects include preparation of purified or highly defined saponin fractions, improved understanding of the relationships between adjuvant activity, toxicity and structure of saponins and formulation of saponins into structures with reduced toxicity such as ISCOMs. Recent developments in the understanding of cellular interactions, cytokine induction and the in vivo localisation of saponin containing formulations will also be reviewed.