A vaccine adjuvant is a substance that can stimulate and/or modulate immune responses induced by a vaccine. It becomes increasingly important in modern vaccine development. However, there are only a limited number of immunostimulating adjuvants for human vaccines. QS-21, a natural saponin isolated from the tree bark of Quilaja Saponaria Molina (QS), is arguably the most potent vaccine adjuvant. It can potentiate a balanced antigen-specific Th1/Th2 response and is a key component of the clinical shingles vaccine (Shingrix); however, QS-21 has its own limitations. To overcome the limitations, we have been focusing on developing practical alternatives to QS-21. Herein we report our progress in developing new saponin-based semisynthetic vaccine adjuvants (VSA-1 and VSA-2), prepared from natural Momordica saponins I and II in one-step. The natural saponins are isolated from the widely available and inexpensive seeds of Momordica cochinchinensis SPRENG. Head-to-head comparison of VSA adjuvants with QS-21 demonstrate VSA adjuvants’ excellent activity in enhancing antigen-specific humoral and cellular immune responses.

Development of saponin-based vaccine adjuvants VSA-1 and VSA-2

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