Decoding the production of saponins offers the possibility of producing more effective and affordable vaccines

The secrets of the core set of genes responsible for decoding the production of saponins have been revealed, offering the possibility of producing more effective and affordable vaccines for saponins, which are effective adjuvants for vaccines, heralding the future of more effective and affordable vaccines.

According to the study, published in the journal Science on March 23, "tree-free" alternatives are still needed to meet the growing demand for saponins while preserving the trees that produce them.

Soapy bottle

Saponin molecules have been used for decades in the food and beverage industry, and recently an important new function has emerged for this substance, as it is considered an adjuvant in vaccines that protect against the coronavirus (COVID-19), malaria and other deadly diseases.

Saponins are obtained from the inner bark of sapy trees (Shutterstock)

Saponins are obtained directly from the inner bark of evergreen species of Quillaja saponaria trees endemic to warm regions of central Chile.

Although production is sufficient to cover the food and beverage industry, vaccine manufacturers are actively working to improve the sustainability of access to this important material and to reduce the environmental impact of its extraction.

Production now relies heavily on extracting saponins from the bark, raising environmental concerns, which is why researchers from John Innes, a leading plant science research institute based in Norwich, UK, have taken a big step forward in tackling the problem.

Using a combination of genomic mining and bioengineering techniques to produce saponins-based pollen materials in the lab without harvesting the material directly from the trees, the Anne Osborne Group (study leader and the group) first sequenced the genome of the soapy glaze tree, then used computational tools to mine for genes and predict which was responsible for the biosynthesis of saponins.

By digging through about 30,16 genes that make up the tree's genome, the researchers were able to trajectorize the shape of the <>-gene chemical compound of saponins, which together produce the enzymes that form the building blocks of nature to produce saponins.

Knowledge of this chemical pathway will enable researchers to develop customized saponin-based adjuvants with a variety of immune-stimulating properties. Dr. James Reed, a postdoctoral researcher at the John Innis Center, said in a press release for the institute: "These are complex molecules that have thwarted attempts to manufacture them on a large scale using chemistry in the laboratory. After many twists and turns, we have now discovered the core set of genes responsible for decoding the production of saponins.

Reconstructing the Chemical Pathway to Formation of a Dwarf Wild Tobacco Plant (Getty Images)

Full Dynamic Path

The identification of 3 other enzymes led to a complete biochemical pathway for another saponin known as Saponin QS-7 which is included in a vaccine adjuvant with proven clinical efficacy, but difficult to purify from the soap tree.

The chemical pathway to form these molecules was reconstructed in a dwarf wild tobacco plant called Nicotiana benthamiana tobacco using a fast and powerful technique called transient fusion expression. This plant is known as a biologically productive host for therapeutic proteins and pharmaceuticals.

The team is already using this instruction manual to try to produce other valuable saponins, including QS-21 saponins, a powerful adjuvant and key ingredient in human vaccines.

He has also partnered with commercial companies that lead the commercialization of the research, and team members are now looking to work with other business and academic partners to scale these quantities further.

Vaccine adjuvants

Vaccine adjuvants are described as hidden aids, an immunosuppressant added to some vaccines to boost the immune response by triggering powerful antibody and T cell responses.

This host plant is capable of bioproduction of therapeutic proteins and pharmaceuticals (Shutterstock)

Until recently, the only adjuvants for clinical use were insoluble aluminum salts or oil in aqueous emulsions, but these adjuvants were not suitable for human use. A vaccine containing an adjuvant based on saponins has therefore been approved for use in humans.

Anne Osborne said, "The COVID-19 pandemic has demonstrated the huge demand for life-saving vaccines. By sequencing the genome of the soapy kalaja tree, we now have an instruction manual that has enabled us to decode how the tree synthesizes these potent medicinal molecules."

"This opens up the possibility of producing known and new vaccine adjuvants based on saponins that are immunocompromised and suitable for human applications in our rapid transient plant expression system."

Desequencing the genome of the soapy tree allows access to the types of saponins required for vaccines and can generate substances designed to deliver optimal immune activity and low toxicity using metabolic engineering.

Whole gene pools provide a solid foundation for improving large-scale commercial saponin production, and sustainable, "tree-free" alternatives to saponin extraction can meet the growing demand for these promising adjuvant vaccines.