Application of Quillaja saponaria extracts as oral adjuvants for plant-made vaccines

Abstract

Extracts from the Quillaja saponaria tree are known to provide immune potentiating responses and, hence, can be useful as adjuvants. Partial purification from the crude (food-grade) extract results in Quil A, which is contained in several veterinary vaccines. Further purification can provide concentrated saponin fractions such as QS-21, which is currently under investigation as a potential adjuvant for use in humans. Purified saponins have proven safe and effective when injected and have significantly enhanced the efficacy of some oral vaccines under clinical investigation. Toxicity of the food-grade extract from Quillaja saponaria has limited its use as a parenteral adjuvant; however, this toxicity seems to be abated when delivered orally. It is commonly used within the food and beverage industries and has no documented toxicity in humans at the present levels of consumption. Use of transgenic plants has been proposed as an alternative system for oral vaccine production and administration, and it is likely that an oral adjuvant will be required in most cases. Food-grade saponins have significant advantages for use with plant-made vaccines and are likely to provide a broad adjuvant effect due to the multiple saponin components. A review of the origin, production, biological activity, toxicity and use in the food industry is provided for Quillaja saponaria extract. Previous evaluation of this adjuvant in preclinical studies with plant made vaccines is discussed and a proposed level of experimental use in humans is provided.

Medicinal plants: Traditions of yesterday and drugs of tomorrow

“…The extracts from the South American tree, Quillaja saponaria, contain triterpenoid saponins (Guo and Kenne, 2000), which are ingredients in an experimental malaria vaccine (Bienzle et al, 2004;Kirk et al, 2004). Partial purification of the crude extract has resulted in the isolation of Quil A, later named Stimulon.…”

Evaluation of three experimental bovine viral diarrhea virus killed vaccines adjuvanted with combinations of Quil A cholesterol and dimethyldioctadecylammonium (DDA) bromide

“…The Q-series of adjuvants, used in this study, are comprised of multiple interchangeable molecules, including Quil A, cholesterol, and dimethyldioctadecylammonium (DDA) bromide. Quil A is an enriched fraction of a tri-terpenoid saponin derived from the bark of the South American tree Quillaja saponaria commonly used in veterinary vaccines (Kirk et al 2004). When Quil A is combined with cholesterol (QAC) it forms helical, nanometer scale worm-like micelles (Mitra and Dungan 2001).…”

Antigen Delivery Systems I

“…Furthermore, Kirk et al (2004) have previously demonstrated the immunogenicity of saponins as potential adjuvants for oral vaccines.…”