Exclusive: Inside the hunt for a vaccine
At 7am on Wednesday, Jane Halton received a text message from one of the world’s largest vaccine manufacturers. She says it gave her goosebumps.
The group, based in London, had been following developments at the University of Queensland (UQ), where researchers have created a potential vaccine for the deadly coronavirus that has caused a pandemic.
“They said, ‘What would it take to manufacture that vaccine?’” Halton tells The Saturday Paper. “‘We have that technology. Can we have a call?’”
Halton is a former secretary of the federal Health Department, and now chair of the Coalition for Epidemic Preparedness Innovations (CEPI), a body started with funding from the Norwegian government and the Bill and Melinda Gates Foundation. The vaccine manufacturer was contacting her because CEPI had funded the coronavirus research at UQ.
Their offer was simple and also hugely surprising: they wanted to make their production lines available to this trial vaccine, halting their own products, at a cost of several million dollars, without any clear financial benefits to themselves. Halton took the call.
The UQ researchers have identified what they call a “candidate vaccine”, which is currently being tested before human trials can begin in June. The team is quietly confident, but the brutal truth is their vaccine may or may not work. In normal times, vaccine development takes years and, once a vaccine is cleared in human trials, producers will take months to tinker with their factories and production lines to make the final product.
But we are not in that world. We are in a world without time, where a private company is willing to take a big risk on a drug that might work.
“This is a company that is prepared to say, ‘All right, we are prepared to burn a bunch of cash,’” Halton says. “It is also an opportunity cost because, fundamentally, they will have to pull other stuff out of production, just in case.”
Halton describes this approach – setting up manufacturing capability while a vaccine is still undergoing clinical trials – as “parallel” processing. If everything goes right, it will mean mass production of a Covid-19 vaccine will already be under way by the time the drug is approved for release.
“If we could start to stand up a production line now – and that’s assuming UQ is ready to go to a first-in-humans trial by, say, June – it would mean that they could actually produce the vaccine as soon as they have it cleared,” Halton tells The Saturday Paper.
On current projections, a three-month head start on production could save more than 100,000 lives.
Halton describes CEPI as “the world’s insurance policy”.
The coalition was officially launched in 2017, although it was operating in an interim capacity after the disastrous 2014 outbreak of the Ebola virus in West Africa.
The World Bank played a key role in CEPI’s establishment, setting up a financial intermediary fund.
A note on the fund, published in September 2017, has proved prescient: “The catastrophic costs of pandemics and zoonotic outbreaks with pandemic potential have a long and notorious history in human civilisation, and presage an increasingly alarming future prognosis.
“… As the threat of pandemics grows in a globalised world where viruses move and mutate faster than ever before, so does the case for increasing the world’s resilience and capacity to prepare, detect and respond to epidemic threats.”
As a first step, Halton and her team went to CEPI’s scientific advisers in 2017 and asked for a list of three of the world’s most dangerous pathogens. The questions were: What was coming for us next? And where did we most need to focus our effort?
The advisers came back with a list of diseases for which “few or no medical countermeasures exist”. This included the Nipah virus, also spread by bats, and Lassa fever, which is commonly spread by rats and mice. The third pathogen on the list was the coronavirus.
Halton was sitting at an American airport in late December when she began receiving text messages and phone calls from her extensive network of public health contacts. They were all about the same thing: a mysterious viral pneumonia outbreak in China’s Hubei province.
“People who have worked on this stuff for years, they all kind of message each other instantly and … they all go” – Halton takes a sharp intake of breath – “and everyone goes, ‘Don’t panic, don’t panic, don’t be silly.’ But everyone has been waiting for the one.”
There is a concept in high-level public health circles about something called “Disease X”. It relates to the fact that while we know something about the viruses that have already run amok in the human population, we don’t really know how to prepare for the next virus – most likely a mutation of a previous outbreak – that behaves differently.
“The CEPI objective is to go from the identification of the pathogen to getting the genome and actually to getting a candidate vaccine in 16 weeks, which is unheard of in terms of the history of this science and in the world,” Halton says.
“Vaccines are unbelievably expensive to develop. I mean, they are really, really, really expensive. So, this whole notion of a public good, making sure there are investments in research and development and early trials on these viruses, that was our starting proposition.”
When Covid-19 broke out, CEPI’s leaders knew there were two projects it had funded that could be marshalled at lightning speed to protect the world from this major threat. One was in the United States and the other was at UQ, led by Professor Paul Young.
More money was needed, however. Almost three weeks ago, Halton wrote to Prime Minister Scott Morrison and the Australian government on behalf of CEPI, urging significant investment.
“We haven’t had a response yet,” Halton says.
On Wednesday, after Halton spoke to The Saturday Paper for this feature, she was appointed by the prime minister to the nation’s Covid-19 Coordination Commission.
This week, the Queensland government, along with the federal government and private sector donors, gave $17 million to the UQ research team. To put that in context, CEPI launched with $US850 million, and has spent almost all of it in two years.
In addition to the UQ proposal, there are 43 other Covid-19 vaccine applications registered with the World Health Organization, but none of them use the unique technology developed last year by the UQ team.
Speaking on Monday, Professor Young explained the importance of parallel processing to him and his 20 researchers.
“Our somewhat radical approach … is to dismantle that linear pipeline and bring large-scale vaccine manufacture forward, essentially to run in parallel with our remaining preclinical and clinical studies,” he said. “… With that approach, we should carve about six months off our delivery time line.”
At the centre of the UQ team’s work is what they call a “molecular clamp”. Essentially, it’s a technology that can “clamp” the virus and render it inert.
Take the coronavirus, for example. The UQ researchers realised the very thing that gives the virus its name – the “crown” of spikes that surrounds the pathogen’s membrane, from the Latin “corona” – can be turned against it.
When the pathogen enters a person’s system, the virus is primed to react to a set of factors. Covid-19 – much like SARS – is looking for a protein that is found in many of our internal organs and in cells on our tongues.
Usually, membranes of the virus and the host cell will repel each other, but the virus that causes Covid-19 has a neat trick – those little spikes act like coiled springs and hold enormous amounts of energy. When that trap is sprung, the spike protein releases energy that draws the two cells even closer, before using the tips of its thorny crown to spear into the host cell, piercing the fatty bilayer and holding the cell until the virus fuses with it.
The virus invades its host the way a pirate boarding party takes a ship.
UQ’s molecular clamp can freeze a synthetic version of the Covid-19 virus in a “pre-fusion” state, thus potentially preventing it taking over the body. This technique still provokes a response from the human immune system, though, which means the body will fight the pathogen.
Last month, the UQ team seeded frozen ovary cells from Chinese hamsters with the candidate vaccine and sent them to a CSIRO lab in Melbourne for animal testing. The next step, in about two months, will include trials on adult human volunteers.
Still, a fully rolled-out vaccine is probably a year away.
“Let me emphasise, and I really do need to emphasise this, this 12-month time line is about as good as we’ll get for a vaccine,” Professor Young told reporters on Monday. “And that is if everything goes according to plan.”
Around the world, other teams are working on different approaches.
In the US, the National Institute of Allergy and Infectious Diseases (NIAID), working with biotech company Moderna, has already started human trials on its candidate vaccine. It says a potential vaccine for first responders could be available by September or October.
In China, Lihua Hou, who registered her country’s vaccine project with the WHO, tells The Saturday Paper that human trials on 108 patients began on March 16 – just two months after the new coronavirus strain was genetically sequenced.
“About half of the subjects were vaccinated with Covid-19 vaccine in this trial,” she says. “Pilot-scale manufacture for this vaccine is not difficult.”
In addition to this work, there are some promising therapeutic trials happening around the world, using existing drugs to treat – but not necessarily prevent – coronavirus infection.
These “off-the-shelf” antiviral drugs already have approval in many countries, as they were developed for HIV treatment (in the case of Kaletra), malaria (chloroquine) or Ebola (remdesivir).
The NIAID director, Dr Anthony Fauci, said remdesivir “showed both prophylactic and therapeutic” capability in rhesus macaques, although testing across trials continues.
Once a vaccine is developed, the next question is how it will be distributed.
CEPI has contracts with its grant recipients that stipulate a product cannot be sold to the highest bidder, although this is not necessarily guaranteed of other players if they succeed.
“There will be a genuine question about where it is manufactured and what the risk is of someone hijacking the lot,” Jane Halton says.
“People will go to war over this. So obviously what you’d look to do is scale up manufacture in a lot of different places.”
Part of that tension rests in who gets the vaccine first. As ever, healthcare workers will be inoculated ahead of everyone else, so they can continue to work. Then vulnerable people, such as the elderly and those with compromised immune systems. After that, the general population will be offered the vaccine.
By Halton’s estimation, billions of doses will be needed.
“These are some of the really big and contentious issues in global health,” Halton says. “How do you make sure that this isn’t the privileged countries of the world looking after themselves and nobody is looking after the poor and the vulnerable? And this is exactly the conversation that’s about to be had and it’s going to be really hard.”
Halton says there are basically two ways to create the herd immunity that will stop the Covid-19 outbreak: vaccines or global sickness.
“The preference is to have a lot of people who have had the vaccine because by definition that means less people will have died.”
CEPI has received an additional €140 million from Germany. Other countries, including Denmark and Finland, have stumped up additional funding, allowing the “world’s insurance policy” to continue its work.
How long will that money last?
“Probably,” Halton says, “until the end of April.”
This article was first published in the print edition of The Saturday Paper on Mar 28, 2020 as "Exclusive: Inside the hunt for a vaccine".
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