Scientists Find a Sustainable Source for a Key Vaccine Ingredient—And It Could Transform Global Vaccine Access

A team of scientists has identified a naturally occurring plant variant that produces QS-21-Rhamnose (QS-21-Rha), a vaccine adjuvant—a substance that strengthens immune response—with immunostimulatory potency comparable to or exceeding the traditionally used version, while offering a dramatically more sustainable production method. This breakthrough could address critical vaccine supply-chain challenges that have limited global vaccine access for years.

What Is QS-21 and Why Does It Matter for Vaccines?

QS-21 is a triterpenoid saponin adjuvant component that has become essential in modern vaccine development. Adjuvants work by activating the immune system more powerfully, helping vaccines trigger stronger and longer-lasting protection against disease. However, QS-21 has been sourced almost exclusively from the bark of mature Quillaja saponaria trees in Chile, creating a severe bottleneck in vaccine production and limiting how many people globally can access vaccines that rely on this ingredient.

The supply problem is stark: producing just 2.2 pounds of QS-21 from traditional bark sources requires harvesting bark from approximately 100 to 120 mature trees. This approach is neither sustainable nor scalable for a world that needs billions of vaccine doses.

How Did Researchers Solve the Supply Problem?

Scientists led by researchers at UC Berkeley, The Scripps Research Institute, and the Access to Advanced Health Institute discovered that a structural variant called QS-21-Rha naturally predominates in the leaves and twigs of young Quillaja saponaria shrubs cultivated in California. Analytical profiling revealed that QS-21-Rha represents more than 95% of QS-21 variants in the aerial biomass—meaning the leaves and branches contain an abundance of this compound.

Using high-resolution mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy, the team confirmed that QS-21-Rha differs from traditional QS-21 by a single chemical substitution: a rhamnose sugar replaces a xylose sugar at the C3 terminal position. This small structural difference turned out to be significant—but in a good way.

Does the New Variant Work as Well as the Original?

Both laboratory and animal studies demonstrated that QS-21-Rha elicits strong adaptive immune responses, with notably robust CD4+ T cell activation. CD4+ T cells are critical immune cells that coordinate the body's defense against pathogens. The immunostimulatory potency of QS-21-Rha was comparable to, and in some cases exceeded, that of traditionally bark-derived QS-21.

This finding is crucial because it means the new variant doesn't sacrifice effectiveness for sustainability—it performs equally well or better while solving the supply crisis.

What Are the Production Advantages?

The shift from bark harvesting to aerial tissue harvesting offers transformative benefits across multiple dimensions:

• Renewable Resource: Young shrub leaves and twigs can be pruned repeatedly without killing the plant, whereas bark harvesting requires felling mature trees that take decades to grow.
• Dramatically Higher Yield: One kilogram of QS-21 can be obtained from pruning just 200 young shrubs, compared with approximately 1,700 kilograms of bark required from traditional sources—equivalent to debarking 100 to 120 mature trees for the same amount of active ingredient.
• Scalability: California cultivation of young Quillaja saponaria shrubs can be expanded more rapidly than waiting for Chilean trees to mature, enabling faster scaling of vaccine production.
• Environmental Sustainability: Pruning young shrubs preserves forest ecosystems and eliminates the ecological impact of harvesting mature trees.

From a production standpoint, this represents a roughly 8-fold improvement in efficiency: the same amount of active ingredient requires harvesting from far fewer plants when using aerial biomass instead of bark.

What Does This Mean for Global Vaccine Access?

The research establishes QS-21-Rha as a chemically defined, immunologically active, and more sustainable vaccine adjuvant candidate. By addressing both supply-chain resilience and production scalability, this discovery could remove a critical bottleneck that has constrained vaccine development and distribution globally.

Vaccines that rely on QS-21 adjuvants have been used in human immunizations, and the ability to produce this key ingredient more sustainably and abundantly could accelerate vaccine development for emerging infectious diseases, expand access to existing vaccines in underserved regions, and reduce the environmental footprint of vaccine manufacturing.

While the research is still in the characterization phase, the findings suggest that QS-21-Rha could transition from laboratory discovery to clinical application, potentially reshaping how vaccine adjuvants are sourced and produced worldwide.