Our Adjuvants

The Quillaja saponaria tree, native to Chile in South America, has bark rich in saponins that have long been developed for pharmaceutical and other commercial applications—most commonly as emulsifiers and foaming agents in cosmetics, beverages, and foods.

More recently, Quillaja saponins have become critical components of vaccines against major public-health diseases. Among them, QS-21 is the current benchmark saponin adjuvant and has been incorporated into the U.S. FDA- and EU EMA-approved vaccines SHINGRIX® and AREXVY®. In addition, Novavax has incorporated its proprietary saponin-based adjuvant, Matrix-M™, into its COVID-19 and flu vaccines. Because these saponin-adjuvanted vaccines elicit strong immune responses, demand for saponins harvested from the Chilean Quillaja tree continues to rise, raising concerns over a sustainable supply. Moreover, the structural instability, dose-limiting toxicity, and low purification yield of QS-21 further constrain its broader application.

ImmunAdd recognizes the value of saponin adjuvants in addressing public-health challenges, but shortages of natural raw materials limit their wider application. The goal of the ImmSygma platform (ImmunAdd Synthetic GlycoMolecular Adjuvants) is precisely this—to overcome such constraints through fully synthetic chemistry and industrial-scale production. ImmSygma IA-05 is a QS-21 derivative in which the branched side chains responsible for toxicity are removed while the key immunologically active structures are retained, achieving excellent aqueous solubility and formulation compatibility. Compared with the conventional plant-extracted adjuvant QS-21, IA-05 offers superior biological tolerability while preserving QS-21-level adjuvant activity. As a single-component, highly purified molecule, IA-05 features a well-defined structure, excellent batch-to-batch consistency, and a sustainable supply, overcoming the long-standing limitations of QS-21—structural instability, dose-limiting toxicity, and low purification yield.

IA-05 elicits potent, long-lasting T-cell immune responses, thereby enhancing vaccine efficacy and protection.

Contributions of our next-generation saponin adjuvant IA-05

Table  Comparison of IA-05 and QS-21

	ImmSygma IA-05	QS-21
Origin	Chemical Synthesis	Extraction from bark of Quillay tree
Stability	Stable as solids (> 3 y) or solution at RT	Easily degraded, stored at low Temp
Purity	Single compound, >97% purity	Heterogenous
Formulation	Liposome or common aqueous formulations	Required liposome or nanoparticle formulations
Dose Range	Mice ≥ 1000 µg Rabbit ≥ 3000 µg Human (tbd)	Mice ≤ 50 µg Rabbit ≤ 100 µg Human ≤ 150 µg
Safety	Well tolerate	Lesion at injection site (w/o liposome)
Immune Response	Th1/Th2, higher cellular response, cross-protection	Th1/Th2
Year Supply	Several hundreds to Kilo-grams (GMP)	Several hundreds grams (GMP)

To address a broader range of adjuvant applications, we have developed a next-generation adjuvant system, ImmSygma IAS-01, composed of two fully synthetic components: the next-generation saponin adjuvant IA-05, and the synthetic Toll-like receptor 4 (TLR4) agonist IA-41. Because the principal components of ImmSygma IAS-01 are all fully synthetic materials, ImmSygma IAS-01 offers a more defined composition than comparable products that rely on natural extracts (for example, GSK’s well-known adjuvant system AS01®), effectively improving product quality consistency and safety, while enabling stable, scalable manufacturing that is not constrained by the harvest season or yield of natural plant sources.

Efficacy in Pre-Clinical Models

In pre-clinical models, ImmSygma IAS-01-adjuvanted vaccines induce strong and durable humoral (antibody) and cellular (T-cell) immune responses, with immunogenicity—and in particular cell-mediated immunity—comparable to or better than current standard comparator adjuvants such as AS01®.

cGMP Manufacturing

Both IA-05 and IA-41 are produced by fully synthetic processes with good manufacturability and scalability. Following formulation development, the two components are manufactured under GMP controls to achieve excellent uniformity, sterility, and production at scale.

Table  Comparison of ImmSygma IAS-01 with Leading Benchmark Adjuvants

	ImmSygma IAS-01	Comparator
TLR 4 agonist	Synthetic MPLA (IA-41)	Native 3-deoxy MPLA from S. minnesota
Saponins	Synthetic saponin (ImmSygma IA-05)	Quillaia extracted QS-21
Formulation & Particle size	Liposome, ≈ 100 nm	Liposome, ≈ 100 nm
Stability	Stable at 4 °C	Stable at 4 °C

AS01® is a registered trademark of GSK Biologicals S.A.