The Australian government has terminated its agreement with Australian biotech company CSL Limited to supply 51m doses of a Covid-19 vaccine being developed by the University of Queensland.
What happened and what does this mean for Australia’s supply of Covid-19 vaccines? We take a closer look.
What was the finding that caused the trial to be halted?
Phase one of the study, involving 216 trial participants, found the vaccine provoked a strong immune response against Covid-19, halting replication. The only side effects in some participants were pain at the injection site, and headaches, which is normal for most vaccines, so safety was not an issue.
The researchers also found the vaccine generated antibodies towards the “molecular clamp”, which led to a false positive result when participants were tested for HIV. University of Queensland researchers pioneered the molecular clamp technology long before Covid-19 existed, patenting it in 2018. A molecular clamp is a chain between proteins that stabilises the shape of proteins in experimental vaccines.
The Covid-19 spike protein has been the focus of UQ and other vaccines because it is the part of the virus that enables it to enter human cells, where it replicates. However, when synthetic versions of these spike proteins are used in vaccines, they become unstable and can change. This means that the immune system may not recognise the protein as Covid-19, and the correct immune response to protect against it won’t be triggered.
This is where the UQ’s molecular clamp comes in. It locks the “spike” protein into a shape, stabilising it, and this allows the immune system to be able to recognise and then neutralise the Covid-19 virus. The clamp chosen by UQ researchers comprises two fragments of the glycoprotein 41 protein found in HIV, as those fragments provided the greatest stability to the spike protein.
Researchers thought the risk of these fragments triggering an HIV immune response was low, but ultimately found during the trial that those who received the vaccine did produce a very low-level antibody response.
Who made the decision to halt the trial and why?
The phase one trial will continue, and participants will be still be monitored over coming months. But the recruitment and participation of thousands more participants for phase two and three clinical trials will not go ahead in December as planned. Phase three trials are the final stage needed before a vaccine is rolled out to the general public.
The decision was a joint one made by the Australian government, CSL, and the University of Queensland researchers in consultation with HIV experts and the national security committee of cabinet. There are a number of reasons for this.
The federal health minister, Greg Hunt, said public support of the vaccine and belief in its safety was essential. The news that the vaccine could trigger a HIV immune response may deter some people, even though it is a harmless response.
“The risk to vaccine confidence was the principal issue here, and we made the decision unanimously as a national security committee, the scientific advice was unanimous, the agreement with CSL not to proceed was mutual,” Hunt said.
If hundreds of thousands of Australians received the vaccine, then began receiving positive HIV test results this would be concerning. Even if the test would later be proven to be a false positive, this may nonetheless cause unnecessary stress to the roughly 1 million people who get tested for HIV each year.
So the other underlying issue was the vaccine’s interference with HIV diagnostic testing.
CSL’s chief scientific officer, Dr Andrew Nash, said if there were no other promising vaccine candidates, then the researchers could be justified in pushing ahead with the vaccine and dealing with the false positives. But other vaccine candidates, including the Pfizer/BioNTech mRNA vaccine, have already produced promising phase three clinical trial results.
Why not just change HIV tests so they don’t respond to the vaccine?
This was an option considered by the UQ and CSL team. They consulted with leading HIV experts to see if current HIV testing technology could be changed. It’s a testament to the quality of HIV diagnostic tests that they could even pick up the low levels of antibodies triggered by the vaccine in the first place.
But Dr Russell Basser, who is part of the research and development team, said: “We worked with HIV specialists and laboratory specialists to map out a different way of screening for HIV.”
“It just seemed to get harder and harder, the more we looked at it,” he said.
“Combined with the fact that the antibody levels declined, though not particularly rapidly at this stage, we felt the burden was probably too great.”
Why not just change the molecular clamp and use something other than the HIV fragments?
This is possible, but it would take time – at least 12 months.
Prof Paul Young, UQ’s head of the school of chemistry and molecular bioscience, said if the virus ends up being endemic within the community, and people require repeat vaccines every year, then there is an option of moving forward with a different molecular clamp down the track.
Basser added: “We’ve left no stone unturned in trying to establish if this could be rolled out in a sensible and reasonable way.” But for now, it doesn’t make sense.
What are the implications for the rollout of Australia’s vaccine program?
Australia had ordered 51m units of the University of Queensland/CSL vaccine, which were expected to be available from mid-2021. With that vaccine now off the table, the government is increasing production and purchase of the AstraZeneca vaccine from 33.8m units to 53.8m units, and units of the Novavax vaccine have been increased from 40m to 51m.
The AstraZeneca vaccine will be manufactured in Melbourne by CSL from early 2021 in monthly batches, so producing extra units of that vaccine will be straightforward. The AstraZeneca vaccine alone could cover the entire Australian population. Phase three clinical trials for the Novavax vaccine are already under way, so that timeline was already ahead of the UQ one.
The prime minister, Scott Morrison, said Australia has “one of the highest ratios of vaccine purchases and availability to population in the world”. He said there was even the potential for a slightly earlier completion of the vaccination schedule, with the government aiming to vaccinate the entire population by the end of 2021.
Are there any concerns for the people involved in the UQ/CSL trial?
The HIV antibodies are harmless. Researchers said the risk of the vaccine triggering a HIV response was outlined on the consent form signed by trial participants. There is no risk to participants of developing HIV. The participants have been regularly updated throughout the trial.
One of the trial participants told the ABC: “We were told clearly at the start there was a tiny HIV inactive fragment, one part of it, which was part of the building block of the vaccine, [and] that there was a chance that we could test positive … We were all well across that, the organisers of the vaccine trial were very good with communicating everything all the way through.”
Who will bear the cost of the UQ vaccine the government had ordered?
The Australian government has invested more than $3.3bn across the four vaccine agreements.
Asked if the investment into the vaccine was money wasted, Morrison told reporters on Friday: “We will continue to support and fund the work that they’re doing on molecular clamp research on vaccines, which has application in many other areas”.
“You need to spread your investments to give as much opportunity for the most successful vaccines to go forward,” he said. “I’m very pleased we backed the world class researchers at the University of Queensland. And my message simply to them today is thank you and all the best with your continued work. You are life savers and we’re incredibly proud of you.”
A CSL spokeswoman said: “The details of our agreement with government remain commercial in confidence. As noted in the ASX press release, CSL does not anticipate this announcement will have any impact on previously provided financial guidance for FY2021.”
How have the researchers working on the vaccine reacted?
UQ’s Paul Young said: “I think there’s probably a single word that sums it up. ‘Devastated’.”
“The last 24 hours or so have been particularly difficult for the team,” he said. “The last 11 months we’ve been living and breathing this particular project, not only members of the team but their families have all been involved so it’s challenging times. But that’s science. It doesn’t always work. We will pick ourselves up, move forward, and develop the next strategy.”
