New study opens unprecedented opportunities for bioengineering vaccine adjuvants

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A molecule derived from the soapbark plant and used as a key ingredient in vaccines, has been replicated in an alternative plant host for the first time, opening up valuable opportunities for the vaccine industry.

A research collaboration led by the John Innes Center is using the recently released genome sequence of the Chilean soapbark plant (Quillaza saponaria) to track and map the elusive genes and enzymes in the complex sequence of steps required to make the molecule QS-21.

Using transient expression techniques developed at the John Innes Centre, the team reconstructed the chemical pathway in a tobacco plant, demonstrating for the first time ‘tree-free’ production of this highly valuable compound.

Our study opens unprecedented opportunities for bioengineering vaccine adjuvants. We can now investigate and improve these compounds to enhance human immunity to the vaccine and develop QS-21 in a way that does not rely on extracts from soap rind.”


Professor Anne Osborne FRS, Group Leader of the John Innes Centre

Vaccine adjuvants are immunostimulants that prime the body’s response to vaccines — and are a key component of human vaccines for shingles, malaria and others under development.

QS-21, a potent adjuvant, is derived directly from the bark of the soapbark tree, raising concerns about the environmental sustainability of its supply.

For years, researchers and industry partners have sought ways to create molecules in alternative expression systems such as yeast or tobacco plants. But lack of knowledge about the complex structure of the molecule and its biochemical pathway in plants has so far hindered this.

Previously researchers in Professor Osborne’s group assembled the initial part of the pathway that forms the scaffolding structure for QS-21. However, the search for the long complete pathway, the acyl chain that forms an important part of the molecule that stimulates immune cells, remains incomplete.

A new study shows that Nature Chemical BiologyJohn Innes Center researchers used a variety of gene discovery methods to identify about 70 candidate genes and transfer them to tobacco plants.

By analyzing gene expression patterns and products supported by the metabolomic and nuclear magnetic resonance (NMR) platforms at the John Innes Center, they were able to narrow down the search to a final 20 genes and enzymes that make up the QS-21 pathway.

First author Dr Laetitia Martin said: “This is the first time QS-21 has been produced in a heterologous expression system. This means we can better understand how this molecule works and how we can address issues of scale and toxicity.

“What’s so rewarding is that this molecule is used in vaccines and my project impacts people’s lives by being able to make it more sustainable. It’s amazing to think that something so scientifically rewarding can bring so much good to society.”

“On a personal level this scientific research has been extremely rewarding. I am not a chemist so I could not have done it without the support of the John Innes Center Metabolomics Platform and the Chemistry Platform.”

The team has partnered with Plant Biosciences Limited PBL (Plant Biosciences Limited) Norwich Limited who are leading the commercialization of the project.

Complete biosynthesis of the potent vaccine adjuvant QS-21 is demonstrated Nature Chemical Biology.

Source:

Journal Reference:

Martin, LBB, etc (2024). Complete biosynthesis of potent adjuvant vaccine QS-21. Nature Chemical Biology. doi.org/10.1038/s41589-023-01538-5.



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