Tree species in Chile raises hope for new Covid-19 vaccine

Along a trail in Chile, forestry experts are cultivating a tree whose bark holds promise for a variety of potential vaccines.

The quillay tree, also known as quillaja saponaria , is a rare evergreen tree native to Chile. This plant has long been used by the native Mapuche people to make soap and medicine.

In recent years, they have been used to successfully produce the world's first Zona vaccine and malaria vaccine, as well as as foaming agents for products in the food, beverage and mining industries.

According to Reuters , now, two molecules of saponins - made from the bark of old quillay trees in Chile's forests - are being used to develop a vaccine against Covid-19 by manufacturer Novavax. The chemicals used to create adjuvants help strengthen the immune system.

Over the next two years, Novavax - a company based in Maryland, USA - plans to produce billions of doses of the vaccine, mainly for low- and middle-income countries. This makes Novavax one of the largest suppliers of Covid-19 vaccines in the world.

Potential new pharmaceutical ingredients

Novavax's adjuvant, called Matrix-M , contains two important saponin molecules. One of them, called QS-21, is found mainly in quillas that have been grown for at least 10 years.

Among the major pharmaceutical companies, only GlaxoSmithKline PLC (GSK) and Novavax bet heavily on QS-21 . This is a relatively new pharmaceutical ingredient.

Desert King International, which now operates the Casablanca plantation, is Novavax's sole supplier of quillay extract and is by far the largest Chilean exporter of quillay.

Wood chips from the quillay tree contain substances used in the Covid-19 vaccine. (Photo: Reuters).

The vaccines containing QS-21 provided by Desert King include Shingrix - a successful GSK vaccine against shingles - and several other promising experimental vaccines. GSK said it is confident of a "sustainable supply" for the QS-21.

The quillay-based adjuvant used in Shingrix is ​​also part of the world's first malaria vaccine, Mosquirix. Despite its low effectiveness, it was approved by European regulators in 2015, and recommended by the World Health Organization (WHO) to be piloted in 2016 because of very high demand.

No other Covid-19 vaccine maker is pinning its hopes on quillay bark extract. Some drug manufacturers develop synthetic alternatives, but it can take years for regulatory approval.

The removal of any ingredient in existing vaccines would also require new clinical research to prove the product is safe and effective.

Find new ways to maximize output

There are currently no reliable data on the number of healthy quillay trees remaining in Chile. Experts and officials are still debating how easily the supply of aged quillas will run out as demand soars.

However, nearly all agree industries that rely on quillay will eventually have to switch to a forest plant, or a laboratory-grown alternative.

A Reuters analysis shows that pressure on the supply of ancient quillas is increasing. Exports of quillay products more than tripled - about 3,600 tonnes per year - in the decade before the Covid-19 pandemic.

Ricardo San Martin - who developed the pruning and extraction process that created the modern quillay industry - said manufacturers must immediately work to create products from young quillay trees and grown in Forest.

Ricardo San Martin - Chilean expert on quillay and its industrial applications - counts seeds on a tree on the campus of the University of California in Berkeley, USA. (Photo: Reuters).

San Martin says he has been working hard to refine the process that could help produce saponins from the leaves and twigs to maximize yields.

Quillay producers and customers say harvesting can resume now without dwindling the supply of older quillas.

'We will continue to monitor the situation in Chile, working closely with our suppliers. But at this point, we are confident in our supply ," Novavax said. The company is also confident that using the supply for 'life-saving vaccines will be prioritized'.

Andres Gonzalez - Desert King's director in Chile - says their line is established enough to produce quillay extracts from old trees, helping to make up to 4.4 billion doses of vaccine by 2022. With supplies from privately owned native forests, they have enough raw material to meet the needs of this year and a third of next year.

Mr. Gonzalez said the company has built a new manufacturing plant, capable of supplying other interested pharmaceutical companies. All are not harmful to the forest. However, he admits 'at some point, these primeval forests will be gone'.

A relatively small amount of quillay extract is needed to produce the vaccine - less than one milligram per dose - but supply is tight due to demand from other industries.

For example, quillay products are used as a natural additive in animal feed, a biopesticide and an agent to reduce pollution in mining.

While there are individual quillas growing outside of Chile, this is the only country where mature quillas are harvested from the forest in large numbers.

The future is full of promise

A few years ago, Massachusetts-based pharmaceutical company Agenus stopped selling the bark extract QS-21 to focus full-time on growing it from quillay plant cells in the lab.

'The QS-21 shortage is a long-standing problem. This was even before Covid-19 started, and we decided to change , 'said Jason Paragas, Agenus vice president of strategic initiatives and growth exploration.

Entrepreneur Gaston Salinas says California-based startup Botanical Solution Inc. can produce QS-21 from scale starting from seed in the lab. The company's ultimate aim is to produce this chemical on a large scale to supply pharmaceutical companies.

'You can't over-exploit Chile's native forests for the sake of developing modern vaccines. You need to find other ways to develop your product, even if it's something very important ," he said.

Seeds of the quillay tree at the University of California at Berkeley, USA. (Photo: Reuters).

Inside the Desert King Plantation, gardeners carefully care for the young quillay plants using fertilizer and abundant water. They are cloned from mature trees of the same family that have dusty gray bark rich in saponins.

According to Desert King's business development manager, Damian Hiley, if all goes well, the plantation could be producing output for an unnamed customer within the next two to three years.

Desert King has his eye on future vaccines, some of which are already in research.

In early 2020, GSK licensed an experimental tuberculosis vaccine containing a QS-21-based adjuvant to the Bill and Melinda Gates Institute for Medical Research. This type gave promising results in the middle of the testing period.

In April, researchers at the University of Oxford announced that a new malaria vaccine containing the Matrix-M adjuvant from Novavax was highly effective in a trial with 450 children in Burkina Faso.

Gustavo Cruz, a researcher at the University of Chile who works with San Martin to industrialize quillay production, said he is confident that quillay producers will find a balance between supply and demand. He is more worried about other threats, namely drought and wildfires.

'Finally, the trees grow back,' he said. 'But there will come a time when they will be gone'.