26 September 2023

The COVID jab: Vaccine research continues

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Nick Sas and Sophie Scott* say Australian COVID-19 vaccine researchers are critical in the global search to find booster shots and ‘next generation’ jabs.

Eunok Lee only became a doctor this year, specialising in mathematics and computer science.

Her colleague, Professor Tony Cunningham, is one of Australia’s most experienced viral immunologists.

But together — along with a team at Sydney’s Westmead Institute for Medical Research — they’re looking into a riddle most people think is already solved: a COVID-19 vaccine.

“We learn from existing ideas,” Professor Cunningham said.

“That’s a key element of science.”

Across the world, eight COVID-19 vaccines have been approved for full use, with Pfizer, AstraZeneca, Moderna — and to a lesser extent Johnson & Johnson and Novavax — dominating the world landscape.

China and Russia have developed and distributed their own Government-backed vaccines domestically, and exported them to select countries across the world.

Yet, as mutant strains of the virus continue to appear, the search for COVID-19 vaccines is far from over.

In fact, according to the World Health Organisation, almost 300 COVID-19 vaccines are still in development; 105 are in human-trial phase and 184 are in the pre-clinical phase.

Scientists and researchers are calling them the “next generation” of COVID-19 vaccines, while other researchers are focused on developing “booster shots” for specific strains of the virus.

And Australian researchers are front and centre in the search.

At least eight locally-developed “next generation” vaccines and “booster shots” are in various stages of development, with Australian researchers also involved in numerous COVID-19 vaccine research projects.

Some are a little unusual, such as a vaccine “patch” being developed out of the University of Queensland and a “nasal spray” vaccine being tested in Brisbane.

Professor Cunningham and Dr Lee’s project itself is focused on something a little different: a T-cell booster shot to help induce long-duration immunity.

“You could say antibodies [the current vaccines] are like the forward troops, and the T-cells are like the reservists,” Professor Cunningham said.

“So if there’s an attack, through a variant strain, the reservists can help move the defence.

“The vaccines we have at the moment [are] protecting us from those variant strains, but they might not in the future, and that’s what we’re preparing for.”

With the help of Dr Lee, who is working on a predictive computer algorithm to help guide the research, the Westmead team is looking long-term and will continue research over the next two years.

‘Chasing the mutants’

Of the local candidates, Flinders University-aligned company Vaxine is the most advanced, with its vaccine Covax-19 in stage 2 human trials in Iran.

The University of Sydney in May received Government funding for its single-dose vaccine, using the tuberculosis vaccine as its base.

At Melbourne’s Doherty Institute, the scope is a little more expansive.

“We’re following the evolution of the virus,” Damian Purcell, head of molecular virology, told the ABC.

“Australia and the world is entering a new phase [in the pandemic] where there’s a new selective pressure for the virus to evolve, what we call ‘immune evasive mutations’.

“You could say what we’re doing now is ‘chasing the mutants’.”

So far, experts say, the current crop of vaccines have stayed ahead of the mutant strains, with research showing they work effectively.

Some of the existing vaccine makers are also developing — and offering — booster shots to heighten protection against infections and new strains.

On Friday, Pfizer, now the primary vaccine in Australia’s rollout, announced it was seeking clearance from US regulators in coming weeks to distribute its own booster shot. It has so far not applied for the same clearance in Australia.

But Professor Purcell — and most of the scientific community — believe the current crop won’t offer protection forever.

It has led the various teams at The Doherty to develop not one new vaccine, but four.

Its lead candidate, a vaccine focused on boosting immunity against the Beta strain — or South African strain — works through a focus on the “receptor-binding domain”. It is being worked on in conjunction with the University of Queensland and CSIRO.

The Doherty is also a part of Monash University’s push to create Australia’s first homegrown mRNA vaccine, following the Victorian Government’s announcement last month.

Both vaccines are set to start clinical trials in October.

Another two vaccines are in very early-stage development; one is created through the “receptor-binding domain” for a common-cold coronavirus.

The last is a booster shot created through an empty virus, or a “virus-like particle”. It is focused on the Beta variant.

Professor Purcell said it was important to continue with a wide scope as the “vaccine book isn’t closed yet”.

“People respond to vaccines in different ways,” he said.

“Say if we have a different variant emerge in Australia, we need to be ready, we can follow it and tune our vaccines in a timely manner to respond. It’s what we call ‘the founder effect’.

“And adapting to that [is] what we’re doing here.”

Professor Purcell said Australia’s vaccine development had come a long way since the start of the pandemic.

“We basically only had one thing in the cupboard: UQ’s clamp technology,” he said. “We all got behind it because it was the best thing we had.

“But, unfortunately, we all know what happened there.”

The clamp, version 2.0

What happened, according to UQ’s Paul Young, was “just devastating”.

After being supported by the Australian Government, in December the UQ team’s molecular clamp vaccine had to “go back to the start” when its vaccine caused false-positive results in HIV tests.

Now, Professor Young said, they were developing a “clamp 2.0”, which is in pre-clinical studies through continued funding by the Coalition for Epidemic Preparedness Innovations (CEPI).

“We’re probably not going to be an answer to the current dilemma,” he said.

“We’re perhaps 18 months away, but we hope to be in a place to contribute to ongoing suppression of the virus as it establishes itself in the community.”

Professor Young said looking longer term, countries would ideally have access to a “large handful of different vaccines”.

“Possibly like the influenza vaccines, but we would perhaps not have to change it as often as the influenza vaccine,” he said.

It’s a concept backed by National Centre for Immunisation Research and Surveillance director Kristine Macartney.

Professor Macartney said we’d need “billions” more vaccines just for the “first round”.

“And then we’ll need the next-generation vaccines,” she said.

“And some will never make it out of the lab. But the positive thing of having 184 vaccines in pre-clinical trials is that these technologies may be used for a range of serious pathogens we’ve never been able to protect against in the past.

“It’s preparing ourselves for the next pandemic.”

*Nick Sas is a digital journalist and producer with the ABC’s Specialist Reporting Team. Sophie Scott is the national medical reporter for the ABC.

This article first appeared at abc.net.au.

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