Antitumor and anti-infectious disease vaccines require adjuvants in order to obtain optimal immunogenicity and therapeutic and protective efficacy. There are few adjuvants available for clinical use that have sufficient potency and acceptable toxicity levels.
QS-21, a natural saponin isolated from the bark of Quillaja saponaria, significantly outperforms other adjuvants in eliciting productive antibody and T cell responses. It has remained the adjuvant of choice in many vaccine trials of cancers, infectious diseases, and degenerative disorders. However, there are several problems associated with the use of QS-21 as an adjuvant, including its scarcity, dose-limiting toxicity, and chemical instability.
In collaboration with the laboratory of chemist David Y. Gin, and more recently with the groups of chemist Derek Tan and radiochemist Jason S. Lewis, we have developed a series of synthetic and semi-synthetic saponin molecules with improved purity, availability, and stability and with diminished toxicity. The impact of these semi-synthetic QS-21 analogues on serologic responses after vaccination with a variety of antigens is now being compared in murine models.