VET-SAP® saponin adjuvant

Saponins are plant tensoactive glycoside compounds, comprising either steroidal or triterpene aglycones linked to carbohydrate chains. The triterpene glycosides isolated from the South American soapbark tree Quillaja saponaria Molina have unique immunostimulating and immunomodulating properties [1, 2].
 

Sources of Quillaja saponins

Different sources of Quillaja saponins are available. Mostly, saponin mixtures or single saponin fractions are extracted from the tree bark, and alternative sources, including cultured plant cell production and recombinant synthesis, have recently emerged: 

− Quil-A® (Croda) adjuvant is a heterogeneous mixture of more than 23 saponin fractions, and each fraction displays different levels of adjuvanticity and toxicity [4, 5].
− VET-SAP® (Desert King International) adjuvant is a purified saponin mixture that contains only the major peaks QS-7, QS-17, QS-18, and QS-21, known to induce both humoral and cell-mediated immune responses [5, 6].
− STIMULON® bark extract QS-21 (Agenus Inc.) contains the most abundant fraction with lower toxicity (QS-21). This purified fraction offers the advantage of enhancing immune responses with a manageable level of reactogenicity [5].
− STIMULON® cultured plant cell QS-21 (SaponiQx) has been developed as a sustainable alternative to bark extraction [7].
− Recombinant QS-21 synthesis using yeasts has been described as an alternative production process to overcome laborious tree bark extraction and ecological concerns [8].
 

Mode of action of Quillaja saponins

Saponins induce a strong adjuvant response to both T-dependent and T-independent antigens [4]. Although the molecular pathways underlying the adjuvant activity of Quillaja saponins are not fully explained, it has been proposed that they act on both T cells and dendritic cells (DCs) [3, 9]:

• The interaction of specific saponin chemical groups with the TCR could deliver a co-stimulatory signal to the T cell, substituting the CD28-CD80 interaction.
• The saponin and antigen (Ag) endocytosis in DCs results in the disruption of the endosomal membrane and release of the Ag for further processing and presentation to T cells.
   

Use of Quillaja saponins in vaccine adjuvant formulations

Free saponins display hemolytic toxicity and hydrolytic instability. Therefore, saponin-based adjuvants are usually formulated with lipids to increase safety and delivery. Several saponin formulations, such as liposomes and phospholipid nanoparticles, have undergone clinical testing [9].

Quil-A®, VET-SAP®, and QS-21 STIMULON® have been extensively used as veterinary vaccine adjuvants [4, 10-12]. QS-21 STIMULON® is currently used in several licensed and exploratory human vaccines, including Shingrix (Zoster vaccine), Arexvy (Respiratory Syncytial Virus vaccine), Nuvaxovid (aka NVX-CoV2373, COVID-19 vaccine), and Mosquirix (malaria vaccine) [7].

​References:

1. Kensil, C.R., et al., 1991. Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex. J Immunol. 146(2):431-7.
2. Press, J.B., et al., 2000. Structure/Function Relationships of Immunostimulating Saponins. Studies in Natural Products Chemistry. 24:131-174.
3. Marciani, D.J., 2018. Elucidating the Mechanisms of Action of Saponin-Derived Adjuvants. Trends Pharmacol Sci. 39(6):573-585.
4.  Petrovsky N. & Aguilar JC., 2004. Vaccine adjuvants: Current state and future trends. Immunol Cell Biol.82(5):488-96. 
5. Cao, L., et al., 2025. Advancements in saponin-based vaccine adjuvants. Medicinal Chemistry Research. 34(9):1817-1832.
6. Talaat., A.M. & Chandrasekar, S. 2022. Neutralizing vaccines against human coronavirus. US 20220/160822 A1 Google Patents, accessed November 2025.
7. Lv, X., et al., 2024. Chemical and biological characterization of vaccine adjuvant QS-21 produced via plant cell culture. iScience 109006.
8. Liu, Y., et al., 2024. Complete biosynthesis of QS-21 in engineered yeast. Nature. 629(8013):937-944.
9. Ben-Akiva, E., et al., 2025. Linking vaccine adjuvant mechanisms of action to function. Science Immunology. 10(104):eado5937.
10. Chandrasekar, S.S., et al., 2020. A Novel Mucosal Adjuvant System for Immunization against Avian Coronavirus Causing Infectious Bronchitis. J Virol 94:10.
11. Futse, J.E., et al., 2024. An adjuvant formulation containing Toll-like Receptor 7 agonist stimulates protection against morbidity and mortality due to Anaplasma marginale in a highly endemic region of west Africa. PLOS ONE 19(8): e0306092. 
12. Singh M. & O’Hagan D., 2003. Recent advances in veterinary vaccine adjuvants. Int J Parasitol. 33:469-78.