Part one: The true story of Australia’s vaccine failure
This story begins three months before the novel coronavirus made its first apparent leap into humans. Two documents from two different continents were published, both of them prepared with no knowledge of the pathogen that was about to change the world.
One – a scientific paper published in the journal Nano – would describe promising breakthroughs in vaccine development and specifically in mRNA. The other – a pandemic planning document created by the Australian Department of Health – provided a necessarily incomplete blueprint for the handling of a future outbreak.
The August 2019 publications made scarcely a ripple at the time. Why should they? It had been seven years since the slow-moving MERS outbreak, a decade since the H1N1 “swine flu” and 15 years since the SARS virus that killed almost 800 people and embarrassed China on the world stage.
The Nano paper, written by scientists at Ghent University in Belgium, declared mRNA an “ideal candidate to trigger immunity against infectious diseases”. It announced that it was “but a matter of time before we will be able to determine which of these mRNA vaccine candidates/strategies enable effective but safe immune responses in humans, hopefully leading to a new generation of vaccines”.
The government document, the “Australian Health Management Plan for Pandemic Influenza”, was the most comprehensive blueprint for a pandemic in the country. It dealt with the flu, however, not a coronavirus, and many of the underlying assumptions about the virality of the pandemic pathogen, such as whether it could spread while hosts were asymptomatic, did not hold up.
These two documents are key to understanding how Australia responded to Covid-19. One went unnoticed while the other was modified on the fly, discarding some of the lessons that ought to have been baked into the nation’s actions during the past 18 months.
Both could have changed the situation the country is now in.
The new year period into early 2020 is important to this story, especially with regards to the creation of a potential vaccine.
On December 31, 2019, the World Health Organization was informed by Chinese authorities that a mysterious pneumonia was circulating in Wuhan. Within the week, the disease was identified as a new coronavirus from the same family of viruses that created SARS and MERS.
By January 11, 2020, Chinese researchers had sequenced the full genome of the virus, sharing it in an open access format.
While the rest of the world slowly woke to the presence of this new threat, scientists from two biotechnology companies in Germany and the United States moved with astonishing speed.
The co-founder of Germany’s BioNTech, Uğur Şahin, created a vaccine candidate in a single weekend in January. In America, Moderna did the same: just two days after the genetic sequence for the virus was released, it finalised a vaccine candidate with the US National Institutes of Health.
Both used a new vaccine platform described in that Nano article. It relied on messenger RNA, the powerful cousin of DNA that can encode genetic information, travel into cells and have that information converted into proteins, the crucial tools of cellular organisms.
The technology has been around since the 1990s but significant advancements during the past three decades have turned mRNA into a plug-and-play platform. All scientists needed was the part of a virus genome that triggered the body’s immune response, which could then be packaged in a particle ready for injection.
For BioNTech and Moderna, developing their vaccine candidates was as simple as cutting out the genetic sequence for the coronavirus spike protein, the thorny outer layer that binds to host cells and becomes the target for the body’s neutralising antibodies.
“The speed of their development meant that mRNA vaccines, given enough funding, would get into efficacy studies early,” Monash University professor Colin Pouton tells The Saturday Paper.
“What was not clear was whether or not they would be sufficiently efficacious. So Covid-19 became an ideal opportunity to test their potential.”
Pouton had already been working on mRNA vaccines here, but without the financial support given to scientists at major pharmaceutical companies. Instead, the Australian government was backing a candidate at the University of Queensland.
About the same time as Moderna and Pfizer were doing their work, scientists from UQ were in discussion with the Coalition for Epidemic Preparedness Innovations about pivoting their funding to developing a vaccine for coronavirus.
By the weekend of January 26, agreements had been signed for the UQ team led by Professor Paul Young and Professor Trent Munro. The project would soon attract millions of dollars in state and federal funding.
Munro, who started his research career as an RNA biologist, was particularly enthused about the university’s patented “molecular clamp” technology. It uses proteins to hold the coronavirus spike in its unsprung position during inoculation, creating a safe target for disease-fighting antibodies.
He was less enthusiastic about mRNA technology at the time. “I wouldn’t have picked RNA,” he tells The Saturday Paper. “There are just so many challenges to thinking about how to scale up RNA, the biology, the uncertainty. So I think all of us as vaccine developers were thinking ‘Look, that’s probably a great idea but is it going to be the one that makes it?’ Probably most of us would have bet not.”
Of course, hindsight always provides an answer. “And thank God, you know, the people at Pfizer and BioNTech and Moderna and CureVac and other places just went hell for leather,” Munro says, “because those have been the ones that saved the world’s bacon, really.”
In the early months of the pandemic, the Commonwealth was still relying on the Australian Health Management Plan for Pandemic Influenza to guide its coronavirus response.
Although the plan was not prepared for a virus such as Covid-19, some of what it says about the critical importance of “case isolation, contact tracing and quarantine of contacts” is relevant.
“Isolation of cases with mild symptoms may be difficult to enforce,” the plan says. “No quarantine premises are available, and use of hotels is problematic.”
The plan had much to say about vaccination, too: “The Australian Government will fast-track assessment and approval of the customised pandemic vaccine; procure vaccines; develop a national pandemic vaccination policy and a national pandemic immunisation program; and communicate immunisation information on the program to the general public and health professionals.”
By April 2020, Colin Pouton and his team at the Monash Institute of Pharmaceutical Sciences had themselves created a candidate vaccine for the SARS-CoV-2 virus using the messenger RNA platform that few believed would win the global arms race for a Covid-19 shot.
But there was no money and no infrastructure to get the product into clinical trials. Pouton would have to wait six months for the Morrison government to offer investment. A grant from the Commonwealth’s Medical Research Future Fund came in October last year, too late to meet Australia’s needs.
Moderna, which had been around for a decade and had mRNA as its sole focus, received a total of $US2.5 billion in “Operation Warp Speed” development funding for its candidate, more than any other vaccine manufacturer in the United States.
Archa Fox, a molecular biologist at the University of Western Australia, says the US government based a lot of its response around faith in the mRNA candidate.
“I think that is a concrete thing that we can point to and say, you know, why was our federal government so conservative?” she says. “The fact the US had invested so much means it wasn’t just a wild and wacky, left-of-centre proposition.”
Through the office of the Chief Scientist of Australia, the federal government established a Rapid Research Information Forum, which produced a report on potential vaccines in May 2020. It was updated again in June last year.
It described mRNA as “a new vaccine technology and although it may be scaled rapidly, this has never been done. No nucleic acid vaccines have been licensed for human use.”
The same month, pharmaceutical giant Pfizer wrote to the Australian government and requested a meeting. A spokesperson for the health department says they had their first formal meeting on July 10, 2020.
“Since this time, there have been numerous formal meetings and phone engagements with the company as part of securing supply of the vaccine for the Australian population.”
The spokesperson said the Science and Industry Technical Advisory Group “also met five times to consider in detail the latest data on the vaccine”.
This group, which was only formally created in August last year, has a clear remit: help the Australian government decide what vaccines to buy and in what numbers.
In June this year, Health secretary and former chief medical officer Brendan Murphy told a senate hearing that the group “provides advice to government and it provides formal advice that then become cabinet submissions to government to procure vaccines”.
He said that on “every occasion” the group made a recommendation, the government procured vaccines in the “doses and amounts” recommended.
According to sources familiar with the advisory group’s meetings, however, that is not quite right in the case of Pfizer – one of just two approved vaccines currently available in Australia – for which the government purchased an initial supply of 10 million doses for delivery in early 2021.
The deal was announced in November last year. According to one source, the government came to the advisory group and said, “This is what has been offered, yes or no?”
This advisory group is meant to direct government, and not the other way around. But as a key source said: “Whether there were other discussions behind that I really don’t know what has happened.”
Asked if the expert group queried whether 10 million doses was enough, the senior science adviser said: “I don’t think we questioned it, but I don’t recall.”
By the time this supply of Pfizer had been offered, the federal government had already announced a deal with both AstraZeneca and the UQ team for 84 million doses of vaccine. The majority – 53 million doses – was to be supplied by the Queensland team through its manufacturing deal with CSL.
The sequence of events between this September announcement and the November Pfizer deal is important. In October – wedged between those two moments – the first warning signs appeared that the UQ product might not make it.
Data began showing that the candidate produced false positives for HIV. The vaccine used a fragment of a protein found in HIV as the molecular clamp, to keep the coronavirus spike protein in place, but it would take months to really understand how and why the tests were showing what they did.
“It’s still difficult to talk about even now,” Munro says. “We always knew it was a risk, and we highlighted that. We let our trial participants know. But we thought it was a pretty low risk and we didn’t expect it until we got our first clinical samples back from trial.
“It was really, really tough, because we had really thrown our lives into this in different ways. We had direct contact with the federal government vaccine advisory group. We’d been giving technical updates to them. It was probably the most difficult part, mentally and emotionally, because there was an element of ‘Have you let the country down?’”
In December last year, the government announced it would abandon the UQ candidate. The major part of its vaccine plan was gone.
News of the UQ disaster led to a “complete reconsideration” of the vaccine rollout, according to one senior source consulted by government.
“We were all pretty crestfallen because we wanted it to work but in drug development you have to be ruthless, you have got to kill your darlings,” they said.
Months before this December scramble, the Morrison government began receiving entreaties from the Australian RNA Production Consortium, a group of scientists pushing for the local production of mRNA vaccines.
Archa Fox, a member of the consortium, said they started talking to the government in the middle of last year.
“We were trying to explain to them how, once you set up the platform, these vaccines could be made but so many other products could be made,” she said. “But they didn’t want to rush in. They wanted to get McKinsey to do the consultation, to get the lay of the land and work out what’s what.”
The consortium was brought in on phone calls with McKinsey & Company, which would go on to receive more than $10 million in Covid-19 related consultancies, including $4.3 million for advice surrounding mRNA vaccine manufacturing in Australia. These reports have not been made public.
“I think it is fair enough to say that, you know, 50 million doses should have been ordered,” Fox says, “rather than 10 million in that first round with Pfizer.”
Another local mRNA expert, who cannot be named, tells The Saturday Paper the government “should have arranged a deal with Pfizer or Moderna earlier”. They add: “I expect their advisers knew very little about the potential of mRNA.”
Even UQ’s Trent Munro, who has now been vaccinated with Pfizer’s product, says “it probably would have been an easy decision to try and go for the higher number of doses upfront; but give the federal government credit: they did negotiate that as part two”.
An additional 30 million Pfizer doses have since been agreed and Moderna will also begin arriving in the country in September.
If there is a theme emerging in the nation’s early response to the pandemic, it is a lack of imagination or even urgency in some cases. This lack of imagination and urgency extends to the role of science in public policy.
“The important discussion is about why do we not have more sovereign capability in the biotech manufacturing space?” Munro says. “Why have companies been leaving Australia for many, many years, for Singapore or Korea or China?”
Munro only moved back to Australia from California in late 2019, after working for a large biotech company over there.
In December 2020, as science reminded the world of its saving grace, Munro and colleagues from the University of Sydney and Melbourne University asked the federal government for $300 million over 10 years to fund dozens and dozens of the nation’s leading vaccine research groups.
Having got so close once, only to be halted by false positives, Munro’s response is a little resigned, almost sarcastic: “We’re waiting to hear on that.”
To read Vaccines, part two: ‘Is this guy serious?’ about how Australia's vaccine rollout has been a series of decisions connected to one original failure, go to Vaccines, part two.
This article was first published in the print edition of The Saturday Paper on Jul 10, 2021 as "Part one: The true story of Australia’s vaccine failure".
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