April 23, 2020 17:45:53
There’s another potential coronavirus vaccine taking that next step to human trials this week.
This time it’s in the UK, where Oxford University researchers have been working on it since January.
It targets the “spikes” on the virus surface with antibodies that stick to them, then the immune system can attack.
Just over 500 people are likely to take part in this trial, all on a voluntary basis.
So, how are these people selected? Why do they do it? And how far away are these vaccines for the rest of us?
How will these initial human trials work?
Whether it’s for a new vaccine or potential drug treatments to tackle COVID-19, trials pass through similar stages.
The first time human testing becomes involved is during phase one, but there’s a lot of laboratory work that goes in before it even gets to this stage; selecting the right compound and gauging how toxic it is.
But, researchers at that preclinical stage still don’t know how people will respond. Cue the small group of healthy volunteers for the first round of testing.
Dr Adam Stewart, from the University of Queensland’s Centre for Clinical Research, said there’ll be regular blood tests to measure how the immune system is responding, looking for antibodies or T-cells to develop.
“Then you want to know how long they stick around, and if they’re going to be long-lasting and effective,” Dr Stewart said.
He said they’re looking at safety primarily at this stage, but also that a vaccine triggers a “rigorous immune response”. That means those antibodies are actually targeting the virus.
“That’s when you move it along the pipeline into the phase two, phase three studies; that’s when you look at it on a larger population scale to see whether patients that are given it actually reduce ability to get disease from it.”
But most vaccines targeting COVID-19 are still at the early phase one stage, including the UK-based trial.
There, the phase one plan will see 510 volunteers vaccinated, half with the COVID-19 vaccine and half with a control test. Phase two will add older people to the mix, first those aged 55-70, then 70-plus.
By phase three, another 5,000 volunteers will be included.
Trials generally go through five stages; first, the preclinical testing period, then three phases of different testing on humans before a final fourth phase, where the vaccine is monitored after its rollout.
So why do people sign up for these trials? And how are they selected?
It’s a little bit about altruism, and a little bit about money, if it’s on offer.
Maximilian de Courten, a global public health expert at Victoria University’s Centre for Chronic Disease Prevention and Management, said phase one trial participants can be paid quite well.
And while it depends on the trial, he said it could be up to $2,000.
But every trial has very strict criteria for inclusion, and that includes both health and psychological testing.
“They also include criteria like have you participated in a trial before, in order to avoid professional phase one trial tourists, going from one centre into the other,” he said.
“But people do want to contribute to the advancement of science and ultimately to protect other people.”
Who is selected also depends on which stage the trial is at, and what they’re trying to do.
Most of the COVID-19 phase one trials starting now or looking to start in the near future (including the Oxford University trial) are asking for healthy people, aged 18-55, to sign up.
That’s because the focus is on checking that it’s safe; monitoring organs like the kidneys, liver, lungs and heart to make sure nothing is going wrong there.
But Professor de Courten said the trial groups can change in later phases to include high-risk groups, potentially the elderly, health care or aged-care workers.
“Particularly in a pandemic or when it’s urgent, you select the high-risk group or the closest target group,” he said.
“To get the full vaccine available for everyone, that will certainly take 12 to 18 months if we are fast.
“If you want to develop an early version for the high-risk then maybe the development is earlier.”
Taking 12-18 months seems like a long time. Is there any way of speeding up the process?
Yes, researchers are definitely trying to do this.
But even the phase one period could take several months or up to two years in normal times, according to Professor de Courten.
“In this pandemic, nobody wants or should wait for that,” he said.
“More and more labs and groups are trying to do a parallel or staggered approach to basically compress the timeline.”
That’s something that’s happening in the UK.
The Oxford University study is already increasing production of its vaccine while the first clinical trial is running, both for later testing and a future, wider rollout.
“By starting vaccine manufacturing scale-up immediately, the team can ensure that enough vaccine doses are available as soon as possible especially for NHS (National Health Service) workers, the elderly, and those with underlying health conditions if the trials prove that the vaccine is safe and effective,” the university said in a statement.
Their best-case scenario is a result from the phase three trial towards the end of this year.
Professor de Courten said it’s usually after phase three where researchers might get their heads around how to produce something. Now it’s far earlier, even in phase one.
“The economic risk is that you might gear up production for something that, two months later they’re saying, actually that’s not the best vaccine,” he said.
“But if you are right, then you have compressed the timeline of normally two to three years to 12 months, if not even less.”
But even a 12-18 month timeline is quick for a vaccine, Dr Stewart said, and realistically there are plenty of barriers in research.
“There are a lot of candidate vaccines that are showing promise out there, but certainly we shouldn’t wait and then in 18 months expect that this is all just going to be perfectly like smallpox, it’s just going to be eradicated,” he said.
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Who has rolled out human trials so far?
Aside from the UK’s latest addition (the vaccine’s official name is ChAdOx1 nCoV-19) there are two in the USA (mRNA-1273 and INO-4800), but both are testing on fewer than 50 people each.
According to a key international vaccine network, the Coalition for Epidemic Preparedness and Innovations (or CEPI), three in China are also at a clinical development phase (Ad5-nCoV, LV-SMENP-DC and a Pathogen-specific aAPC).
But there are many more in the works CEPI found 115 potential vaccines for COVID-19 in various stages of development at the start of April.
That includes Australian candidates, like the one being produced by the University of Queensland, where researchers have been working since January on a potential vaccine.
Human trials for this vaccine are expected in the third quarter of this year, so between July and September.
But Australia also has some human trials set to launch sooner.
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Clinical trial company Nucleus Network will run phase one testing for a US company, Novavax, out of its Melbourne and Brisbane clinics.
The trial of another candidate (this one is NVX-CoV2373) is expected to start in mid-May and early results will be ready in July.
And Australia’s lower rate of community transmission so far (especially compared to parts of Europe and the US) could actually help vaccine trials here.
Dr Stewart said while there’s still a need to test widely, it appears a large proportion of people in Australia won’t have been exposed and people with no detectable exposure to COVID-19 are often what researchers want at first.
“They’re the people you’re trying to target because, obviously, it is likely that if you’ve been exposed or even had an illness, you may have developed an immunological response,” he said.
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If we do get a vaccine, how would it be rolled out?
In normal times, the vaccine would be approved by regional bodies like the Therapeutic Goods Administration (TGA) in Australia, or the European Medicines Agency (EMA).
Then they’d be allowed to be rolled out in those specific markets.
But during an unprecedented pandemic, this could all change.
Dr Stewart said the registration processes are very similar between Western agencies.
“The data they’d be collecting is near-identical,” he said.
“These are special times and if there’re early signs of benefit of any of these vaccines there’ll certainly be countries around the world that will be very keen to disperse that.”
And it’s not just finding something that works and getting it out to people that’s a concern. It’s producing potentially billions of doses.
Professor de Courten said while he foresees a staggered rollout, exactly how the eventual candidate is produced will have to be solved in the coming months and years.
“Some of them, the influenza vaccine for instance, is produced using eggs,” he said.
“For COVID-19, there wouldn’t be enough eggs in the world.
“The production question is a very serious one. So there is one thing of finding an effective vaccine, then not being able to produce it, so you need to solve those problems.”
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