Multiple saponin compounds exhibit adjuvant activity 3912

Description QS-21 is a saponin compound extracted from South American evergreen tree bark. The ability of QS-21 to induce robust cellular and humoral immunity as an adjuvant led to its evaluation in multiple vaccine trials. However, high toxicity seen following purification hinders the widespread use of QS-21 and has resulted in the search for suitable alternatives. We evaluated a group of 14 saponin compounds as alternatives to QS-21. Ten of the compounds were chemically synthesized as novel derivatives from the saponin lablaboside F, whereas the remaining 4 were extracted from soybeans. C57BL/6 mice were immunized intramuscularly with each compound mixed with ovalbumin (OVA) protein in a prime-boost strategy. Compounds S1, S5, A1, A2, and V produced significantly increased OVA-specific total IgG antibodies 2 weeks post-boost as compared to control mice. In addition, S1 and S5 elicited significantly increased OVA-specific IgG1 antibodies as compared to control mice, whereas A1, A2, and V did not. S5 also produced increased OVA-specific IgG2c antibodies, but the levels did not reach significance. Finally, S1 displayed significantly increased cellular toxicity 24 hrs post-treatment in vitro as compared to treatment with media, whereas S5, A1, A2, and V did not. These results illustrate that saponin compounds S1, S5, A1, A2, and V exhibit adjuvant activity. Our results demonstrate multiple saponin compounds safely elicit humoral immunity and could serve as suitable alternatives to QS-21. Funding Sources Supported by RO1 AI169505 and RO1 AI167249 Topic Categories Vaccines and Immunotherapy (VAC)