HIV false positives terminate Aussie vaccine

UQ team ‘devastated’ by halt to COVID-19 vaccine

"Devastated." That is the word Professor Paul Young from the University of Queensland uses to describe the canning of Australia's most promising COVID-19 vaccine.

Although the vaccine's revolutionary molecular clamp technology returned a robust immune response to coronavirus in 216 trial recipients in the Phase 1 trial, volunteers were warned that fragments of a protein derived from the HIV virus could produce antibodies, or a partial immune response to HIV.

Although there was no possibility the participants could acquire HIV, the vaccine had the potential to interfere with existing HIV testing procedures.

Dr Marianne Gillard, Minister Kate Jones, Professor of Virology Paul Young (centre), Dr Keith Chappell, and Dr Dan Watterson, in the Molecular Virology Lab. Picture: Liam Kidston
Dr Marianne Gillard, Minister Kate Jones, Professor of Virology Paul Young (centre), Dr Keith Chappell, and Dr Dan Watterson, in the Molecular Virology Lab. Picture: Liam Kidston

"For the last 11 months we have been living and breathing this, it's been a challenging time for us, and our families. The team is devastated with the decision, but we understand the need to make it," Prof Young said.

In an exclusive interview with Professor Young just last month as results were coming in from the phase one trial, Prof Young, a virologist of 40 years, said safety was paramount.

"It's critical. There is no point in deploying a vaccine large-scale in the human population when we're not absolutely confident that it's safe. So that will not happen. And we don't cut corners when it comes to safety."

Prof Young said the team had been put under enormous pressure from all quarters given the time pressure to come up with a vaccine.

"The pressure has been enormous. The folks in the lab have been working as they say, in the classics 24/7 and in shifts. In March, when physical distancing was really a very important component of all activity in Australia, we actually split the group in two, because the possibility was that if anyone went down with COVID-19, then we would have to quarantine all of the groups. So we split and we didn't come into contact and we were able to run the project with those two relatively large teams."

The UQ technology had been in development for years because a pandemic was expected.

"COVID-19 was absolutely predictable, perhaps not at the scale, although we were always due for a full pandemics scale virus. But there've been viruses and bacteria and parasite emergencies over the last 20, 30 years regularly, causing epidemics cross national boundaries and occasionally spread around the world like the flu did in 2009."

The UQ vaccine used a technology called a molecular clamp. Science can be hard to explain, but the SARS-CoV-2 virus is unstable and for a vaccine to target the spike protein, the protein that attaches itself to cells to allow it to enter can cause infection, had to be 'locked' into shape to induce the immune response. The team had a choice of molecular clamp proteins from various viruses but chose protein fragments from the HIV virus. On its own it is harmless but it provided 'greatly enhanced stability'.

Professor Paul Young with Health Minister Greg Hunt during a visit to the National Biologics Facility at the University of Queensland, St Lucia. Picture: Sarah Marshall
Professor Paul Young with Health Minister Greg Hunt during a visit to the National Biologics Facility at the University of Queensland, St Lucia. Picture: Sarah Marshall

It was tested on hamsters first in April.

"We can't have hamsters in Australia. So we had to do these studies overseas in the Netherlands. And in this model, when you challenge a hamster with that live virus they get sick, they get a pulmonary infection rather like humans do. So, we were able to immunise those with our vaccine and show that we could protect them. We also had to show that it was as a drug product, that it was just safe to deliver so that it didn't have any other alternative deleterious effects when delivered. So we did toxicology studies as well. So with all that preclinical work, we put together a package of information that went to an ethics committee, who then gave us the sign-off to go into our phase one clinical trials, which began in July."

The team knew there was "a theoretical risk" that the protein could produce HIV antibodies in humans and warned the 216 trial recipients of the possibility and that warning was included in the consent forms.

"We warned of it, but did not expect it," Prof Young said.

Volunteers in the trial have been reassured there is no risk to their health.

"We want to reassure that there is no connection to HIV, it is a cross reaction with a subset of HIV diagnostic tests," Prof Young said.

Given what was at stake, Dr Andrew Nash, chief scientific officer at CSL, the company enlisted to manufacture the proposed 51 million doses of the UQ vaccine, said no-one could afford to have the vaccination program undermined by the spin that could come from the link to HIV.

"Public confidence was an important part of the decision and we wanted to make sure we didn't allow that to happen," Dr Nash said.

Rather than a failure, this decision proves the "scientific process was working" according to Federal Health Minister Greg Hunt.

"The scientific advice is the risk to vaccine confidence was the principal issue here.

"We planned in all our contracts for the potential either to discontinue based on the scientific advice, or to expand the number of vaccines, so we are increasing our Astra Zenica purchasing by 20 million units to be produced onshore here in Australia. At the same time the Novavax contact has allowed us to expand," Mr Hunt said.

Chief Medical office Prof Brendan Murphy said Australia was in the "wonderful position where we can take our time to go through the normal regulatory process, we don't need emergency approval, we are in a good position because we have controlled the virus, so I am very confident about the successful vaccination strategy we will be facing next year."

Australia is expected to roll out extra doses of over 140 million units of the Astra Zenica, Novovax and Pfizer vaccines in March next year to front line health workers and high risk groups first.

Prime Minister Scott Morrison said: "at the end of the day, the Therapeutic Goods Administration - like with any vaccine in Australia - it must have their tick-off. Without the tick, there's no jab, when it comes to vaccines in this country. That is true for the COVID-19 vaccine, as it is true for any other vaccine that is administered here in Australia."

As for Prof Young and his team, they are not proceeding with the vaccine and to redevelop the clamp with another molecule would take another 12 months, but which time more advanced vaccines would have already been rolled out.

"We will pick ourselves up and go forward," he said.

The underlying technology will now be focused on developing vaccines for other pathogens.

Originally published as UQ team 'devastated' by halt to COVID-19 vaccine