Saponin

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Saponin Adjuvant

Saponins are natural glycosides of steroid or triterpene which are widely distributed in the plant and exhibit many different biological and pharmacological activities such as antiphlogistic, antiallergic, cytotoxic, antitumor and antitumor-promoting, antiviral and so on. They can activate and modulate the mammalian immune system, therefore attract significant interest as immunological adjuvants for use in vaccines. The most extensively used saponin-based adjuvants are saponin vaccine adjuvant and its derivatives QS-21, isolated from the bark of the South American tree Quillaja saponaria. Immunostimulatory effects of saponins from Quillaja saponaria have been known since nearly 100 years ago.

Immunostimulation by Saponin Adjuvants

Saponin adjuvants show a strong adjuvant potential which appears to be associated with their ability to induce cytokine production. Depending on their oligosaccharides, saponins may induce Th1 or Th2 immunities, thus, the mechanisms of action (MOAs) must be established only after the type of immune response has been certainly identified, and also induce strong cytotoxic CD8⁺ lymphocyte responses and potentiate the response to mucosal antigens. The most widely used triterpene saponin adjuvants like QS-21 may act independently or in concert on T cells and dendritic cells, via receptor-mediated and non-receptor-mediated mechanisms. It can induce either proinflammatory Th1/Th2 or sole anti-inflammatory Th2 immunities. QS-21 comprises four structural domains, with a central quillaic acid triterpene core flanked by a branched trisaccharide, a bridging linear tetrasaccharide, and a glycosylated acyl side chain. About the analysis of QS-21 structure, studies have shown that imine-forming carbonyl groups are needed for T cell activation leading to induction of Th1/Th2 immunities. Although saponins with different triterpenoid aglycons and oligosaccharide chains can activate DCs to induce Th1/Th2 immunoresponses, fucopyranosyl residues from their oligosaccharides by binding to the DC-SIGN receptor can bias DCs toward a sole Th2 immunity.

Fig. 2 Schematic diagram of QS-21.

The Potential of Saponin Adjuvants

Saponin-type adjuvants have hydrophobic domains from which their surface-active properties arise. They are ideal for use in subunit vaccines and vaccines directed against intracellular pathogens as well as for therapeutic cancer vaccines due to their unique capacity which can stimulate both the Th1 immune response and the production of cytotoxic T-lymphocytes (CTLs) against exogenous antigens. Quil A has been used successfully for veterinary applications. In a trial with HIV-1 env antigen, QS-21 was able to allow a significant dose reduction for the antigen and also enhanced proliferative T-cell responses but not CTL. QS-21 has also been claimed to perform as an adjuvant for DNA vaccines, following both systemic and mucosal administration. But saponin-based adjuvants have some drawbacks such as high toxicity, undesirable haemolytic effect and instability in aqueous phase, which limit their use as adjuvant in the human vaccine development. It has encouraged the research for saponin-based adjuvant from other kinds of natural products. QS-21 significantly outperformed the other classes of adjuvants including glucan formulations, peptidoglycans, amphophilic block copolymers, bacterial nucleosides and bacterial lipopolysaccharides to better serve the broad market.

Creative Biolabs is a leader in the field of vaccine adjuvant development and has focused on the saponin adjuvants for many years. We have experts who are able to help you with the development of the saponin adjuvants for use in vaccines. If you are interested in our services, please contact us for more details.

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Reference

1. Dante J. Marciani. (2018). “Elucidating the Mechanisms of Action of Saponin-Derived Adjuvants.” TRENDS PHARMACOL SCI 39 (6), 573-585.

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