Allison Martell, Aislinn Ling

CASABLANCA (Chile) – Behind a chained wooden gate, forestry specialists are tending a plantation saplings whose bark promises potent vaccines.

Quillay trees (also known as Quillaja Saponaria) are rare Chilean evergreens that were used for soap making and medicinal purposes by indigenous Mapuche peoples. In recent years, they have also been used to make a highly successful vaccine against shingles and the world’s first malaria vaccine, as well as foaming agents for products in the food, beverage and mining industries.

Now two saponin molecules, made from the bark of branches pruned from older trees in Chile’s forests, are being used for a COVID-19 vaccine developed by drugmaker Novavax (NASDAQ:) Inc. They are used in the manufacture of adjuvant.

Novavax, a Maryland company, plans to make billions of vaccines over the next two-years, mainly for countries with low and moderate incomes. This would allow Novavax to become one of the biggest COVID-19 vaccine producers in the world.

Industry officials and experts are not able to provide reliable information on the number of Chilean quillay tree health. They are also divided over how fast rising demand for older trees could deplete their supply. However, almost everyone can agree that the quillay industry will need to shift to either lab-grown plants or to trees grown in plantation.

A Reuters analysis shows that older trees are under increased pressure. This is according to ImportGenius, a trade data provider. In the decade preceding the pandemic, exports of quillay products increased more than threefold to over 3,600 tonnes annually.

Ricardo San Martin is the man who created the extraction and pruning process which gave rise to the quillay market. Accordingly, producers need to immediately make quillay products with younger plants.

“My estimate four years ago was that we were heading towards the sustainability limit,” he said.

San Martin stated that he worked tirelessly through the COVID-19 pandemic at his Sea Ranch cabin to perfect a method to produce saponins, leaves, and twigs to increase the yield.

“I am working as though this needs to be done yesterday,” said San Martin, who is also sponsoring a project in which drones would count quillay trees in remote and hard-to-access forests, to determine how many are left.

According to Quillay’s producers, their customers and the farmers of Quillay, the harvest is possible for the moment without reducing the supply of older trees.

“We continue to monitor the situation in Chile, in close collaboration with our supplier, but at this time we are confident in our supply,” Novavax said in a statement to Reuters. The company also said it was confident that uses such as “life-saving vaccines will be prioritized.”

The desert-plant extract company Desert King International Ltd, which runs the Casablanca plantation, is Novavax’s sole supplier of quillay extracts and Chile’s largest quillay exporter by far.

The company’s manager in Chile, Andres Gonzalez, told Reuters it is set to produce enough quillay extract from older trees to make up to 4.4 billion vaccine doses in 2022. They have sufficient raw material from native forests that are privately owned to supply the demand for this year’s and next part of the year, he stated.

Gonzalez claimed that San Martin was a consultant for the company and the new manufacturing plant has been built. The facility can also supply other pharmaceutical firms, all while preserving the environment.

He acknowledged, however, that “at some point these native forests will come to an end.”

“We want to start having very productive plantations, and we are working on that,” he said.

It takes a small amount of quillay to produce vaccines. The dose is just one milligram. But, due to the high demand from other industries, this supply will be limited. You can use quillay products as, for example, an animal feed additive, a biopesticide or a method to lower pollution in mines.

Although quillay trees can be found outside Chile, it is only in Chile that mature quillay can be harvested from its forests in large numbers.

A PERFECT INGREDIENT

Novavax’s adjuvant, known as Matrix-M, contains two key saponin molecules. QS-21 is the more difficult of these two molecules to find because it’s only found in trees at least 10 years old.

Only GlaxoSmithKline PLC (NYSE:) and Novavax, two of the largest pharmaceutical companies have placed a large amount on QS-21, an innovative pharmaceutical ingredient.

GSK’s highly successful vaccine against shingles, Shingrix, and several other promising experimental vaccines contain QS-21 supplied by Desert King. In a statement, GSK said it has “no specific challenges relating to sustainable supply” of QS-21.

The quillay-based adjuvant used in Shingrix is also part of the world’s first malaria vaccine, Mosquirix. Although it is not very effective, European regulators approved it in 2015. It was recommended by WHO to be piloted by WHO in 2016, due to the dire need.

Other COVID-19 vaccine makers are not relying upon quillay bark extracts. While some drugmakers may be developing new synthetic options, these alternatives could still take many years to receive regulatory approval. To replace any vaccine ingredient, new clinical trials would be required to verify safety and effectiveness.

Agenus, a Massachusetts-based pharmaceutical firm (NASDAQ:), stopped selling bark-derived QS-21 many years ago in order to concentrate on growing it from quillay plants cells in a lab.

“The shortage of QS-21 has been an issue for a while,” said Jason Paragas, Agenus vice president of strategic initiatives and growth exploration. “We saw it before COVID, and we made the hard decision that we had to change.”

Paragas stated that it was too early to predict when an alternate could be available.

Gaston Salinas (entrepreneur), said Botanical Solution Inc in Davis, California can now produce QS-21 starting from seeds. The company aims eventually to make the chemical large-scale to be supplied to pharmaceutical companies.

“You cannot afford to over-exploit the native Chilean forest because of a desire to develop modern vaccines. You need to find other ways to develop your products, even if it’s something so important, ” he said.

A VIEW TOWARDS THE FUTURE

Gardeners tend to young trees inside the gates of Desert King’s carefully protected plantation. They use fertilizers and plenty of water. The clones were made from their full-grown counterparts, whose greyish brown bark contained a lot of saponins.

If all goes well, the plantation could be producing for one customer in two to three years, according to Desert King’s business development manager Damian Hiley. He refused to identify the company.

Desert King is looking at future vaccines. Some are already being developed.

In early 2020, for instance, GSK licensed an experimental tuberculosis vaccine that contains GSK’s QS-21-based adjuvant to the Bill and Melinda Gates Medical Research Institute. The results of a midstage trial were promising.

And in April, researchers at Oxford University announced that a new malaria vaccine containing Novavax’s Matrix-M adjuvant appeared to be highly effective in a trial involving 450 children in Burkina Faso.

Gustavo Cruz is a University of Chile researcher who collaborated with San Martin in industrializing quillay production. He said that he trusts the quillay producers to handle supply and demand. Other threats, such as drought or fire, are more concerning to him.

“The trees do eventually regrow,” he said, “but there comes a time when they don’t anymore.”

(Aislinn Leing reported from Casablanca, Allison Martell was from Toronto. Nivedita Balu, Bangalore added reporting. Caroline Humer and Peter Henderson edited. Julie Marquis also contributed to editing