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 Quillay trees, technically known as Quillaja saponaria, are rare
evergreens native to Chile that have long been used by the
indigenous Mapuche people to make soap and medicine. 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 Inc. The chemicals are used
to make adjuvant, a substance that boosts the immune system.
Over the next two years, Maryland-based Novavax plans to produce
billions of doses of the vaccine, mostly for low- and middle-income
countries, which would make it one of the largest COVID-19 vaccine
suppliers in the world.
With no reliable data on how many healthy quillay trees are left in
Chile, experts and industry officials are divided on how quickly the
supply of older trees will be depleted by rising demand. But nearly
everyone agrees that industries relying on quillay extracts will at
some point need to switch to plantation-grown trees or a lab-grown
alternative.
A Reuters analysis of export data from trade data provider
ImportGenius shows that the supply of older trees is under
increasing pressure. Exports of quillay products more than tripled
to more than 3,600 tonnes per year in the decade before the
pandemic.
Ricardo San Martin, who developed the pruning and extraction process
that created the modern quillay industry, said producers must
immediately work toward making quillay products from younger,
plantation-grown trees.
“My estimate four years ago was that we were heading towards the
sustainability limit,” he said.
San Martin said he has toiled through the COVID-19 pandemic in the
basement of his oceanfront cabin in Sea Ranch, California, to refine
a process that could help produce saponins from leaves and twigs in
order to maximize 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.
Quillay producers and their customers say the harvest can continue
for now without decimating 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. With new supplies from privately
owned native forests, they have enough raw material to meet demand
for the rest of this year and part of next, he said.
Gonzalez said the company, where San Martin is a consultant, has
built a new production plant and has the capacity to supply other
interested pharmaceutical firms - all without harming the forests.
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.
A relatively small volume of quillay extract is required to make
vaccines - just under one milligram per dose - but the supply is
stretched by the demand from other industries. Quillay products are
used, for instance, as a natural additive in animal feed, a
biopesticide and an agent to reduce pollution in mining.
Individual quillay trees grow outside of Chile, but Chile is the
only country where mature quillay is harvested from forests in large
quantities.
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AN ELUSIVE INGREDIENT
Novavax’s adjuvant, known as Matrix-M, contains
two key saponin molecules. One of those, called
QS-21, is more difficult to access because it is
found mainly in trees that are at least 10 years
old.
Among major pharmaceutical companies, only
GlaxoSmithKline PLC and Novavax have bet heavily
on QS-21, a relatively new 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. Despite low efficacy, it
was approved by European regulators in 2015 and recommended for
pilot introduction by the WHO in 2016 because of dire need.
No other COVID-19 vaccine manufacturers are relying on quillay bark
extracts. Some drugmakers are developing synthetic alternatives, but
these could be years from regulatory approval. Switching out the
ingredients in any existing vaccine would require new clinical
studies to prove the product is safe and effective.
The Massachusetts-based pharmaceutical company Agenus stopped
selling bark-derived QS-21 several years ago to focus full-time on
trying to grow it from quillay plant cells in a laboratory.
“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 said it is too soon to say when an alternative could be
ready.
Entrepreneur Gaston Salinas said his Davis, California-based startup
Botanical Solution Inc can already produce QS-21 from quillay tissue
starting with seeds in the lab, and aims to eventually produce the
chemical on a large scale to supply 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.
AN EYE TOWARD THE FUTURE
Inside the gate of the carefully guarded Desert King plantation,
gardeners carefully tend to the young trees using fertilizers and
bountiful supplies of water. They were cloned from full-grown
cousins whose dusty gray bark was especially rich in 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 declined to name the company.
Desert King has its eye on future vaccines, some already in the
works.
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. It showed
promising results in a mid-stage trial.
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, a researcher at the University of Chile who worked
with San Martin to industrialize production of quillay, said he
generally trusts quillay producers to manage supply and demand. He
is more worried about other threats - specifically drought and fire.
“The trees do eventually regrow,” he said, “but there comes a time
when they don't anymore.”
(Aislinn Laing reported from Casablanca; Allison Martell from
Toronto. Additional reporting by Nivedita Balu in Bangalore. Editing
by Caroline Humer, Peter Henderson and Julie Marquis)
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