Structural Effect on Adjuvanticity of Saponins

We
have prepared a number of saponin-based vaccine adjuvant candidates.
These unnatural saponins have a different terminal-functionalized
side chain incorporated into the glucuronic acid unit that is attached
to a triterpenoid core at its C3 position. The semisynthetic saponin
adjuvants have shown significantly different immunostimulatory activities,
suggesting that the structure of the side chain, triterpenoid core,
and oligosaccharide domain together orchestrate saponin adjuvant’s
potentiation of immune responses. Among these new adjuvant candidates,
VSA-2 (5b), a derivative of Momordica saponin (MS) II, showed consistent enhancement of immunoglobulin
G2a (IgG2a) production when it was in formulation with either ovalbumin
or recombinant hemagglutinin B (rHagB) antigen. With rHagB antigen,
it induced a significantly higher IgG2a response than the positive
control GPI-0100, a well-studied semisynthetic saponin adjuvant mixture
derived from Quillaja saponaria Molina
saponins, known for its ability to induce a balanced Th1/Th2 immunity.
These results confirm that Momordica saponins are
a viable natural source to provide potent saponin adjuvants after
simple chemical derivatization and identify VSA-2 (5b) as another MS-based promising immunostimulant lead owing to its
distinctive ability in potentiating the IgG2a response.