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‘It’s not hype’: COVID vaccine technology to fight another deadly virus, then cancer

By Liam Mannix

The vaccine technology used to fight COVID-19 could soon protect people from another deadly respiratory virus, and trials are under way to determine whether it might also be effective against cystic fibrosis and melanoma.

An mRNA vaccine for respiratory syncytial virus (RSV) – a highly contagious infection that can be life-threatening to babies and the elderly – could be in medical clinics before the end of the year.

The technology behind mRNA vaccines is being adapted to tackle new diseases.

The technology behind mRNA vaccines is being adapted to tackle new diseases.

In January, Moderna reported promising results from a large, late-stage clinical trial of its RSV vaccine: it was 83.7 per cent effective at preventing symptomatic RSV in older adults. Trials of the vaccine in pregnant women and infants are now under way.

A more ambitious therapy is close behind: a vaccine for melanoma.

The company reported strong results from a trial in December and is considering filing for emergency approval this year.

“It’s not hype,” says Associate Professor Traude Beilharz, head of the RNA systems biology lab at Monash University. “The technology is amazing.

Haley Chartres with son Louis, who had a brush with RSV.

Haley Chartres with son Louis, who had a brush with RSV.Credit: Scott McNaughton

“It’s going to be incredibly expensive. But the promise is enormous.”

For Haley Chartres, an RSV vaccine cannot come soon enough. Her son Louis picked up the virus last year. Within days, he was gasping for air.

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“He basically got to a point where he was in my arms and he went really limp. And the colour went from his face,” Chartres says.

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An ambulance rushed Louis to hospital, where he eventually recovered with oxygen and treatment. But it’s something no parent should have to go through, Chartres says.

“One hundred per cent, I support a vaccine. Anyone who saw a child struggle like that would agree with me.”

The dream for biotech companies and governments pouring money into mRNA is a repeat of the extraordinary success of the COVID-19 vaccines: effectiveness rates approaching 95 per cent, beating both older protein and newer viral-vector technologies.

Those rates are yet to be fully realised. The data from Moderna’s RSV vaccine is promising, but no better than vaccines being developed by GSK and Pfizer using traditional technologies.

And mRNA – or messenger ribonucleic acid – comes with a big unknown: how long will it provide protection?

“The mRNA vaccines have not performed that well in terms of longevity with COVID. We need to know whether this particular vaccine is different,” says Professor Ian Barr, deputy director of the World Health Organisation’s Collaborating Centre for Reference and Research on Influenza.

Other companies are now testing mRNA vaccines for influenza, CMV (cytomegalovirus), Zika and dengue viruses. But infectious diseases are merely the low-hanging fruit for mRNA.

These vaccines introduce an enemy to train the immune system, essentially the same thing as older technologies. The next diseases on the hit-list take advantage of mRNA’s ability to do things other drugs can’t.

“If anybody ever thought mRNA was just for COVID, the last six months have proven that mRNA is a transformational therapeutic that can be brought to bear on so many diseases,” says Moderna’s chief medical officer Dr Paul Burton.

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In early 2018, a doctor slid a needle into Pamela Morey’s arm and injected a small ampoule of mRNA.

Morey had advanced melanoma, where cells turned cancerous after accumulating a cluster of DNA mutations. Despite several operations to cut tumours out, the cancer kept coming back.

“They told me they couldn’t guarantee it wouldn’t come back in my lungs or brain – and if it comes back there that’s Goodbye Charlie, you know,” she says.

Weeks before her jab, scientists sliced out a chunk of her tumour and sequenced the genetic mutations driving the cancer: the mRNA contained those genetic codes in a trial of what scientists call a “personalised cancer vaccine”.

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Combined with another drug that boosted the immune system, the mRNA essentially trained Morey’s immune system to hunt and kill any tumour cells circulating in her body. The trial cut the risk of cancer recurrence or death by 44 per cent compared to standard care. Morey has been cancer-free for three years.

“It’s not a cure for everybody,” says Professor Georgina Long, co-medical director at Melanoma Institute Australia and one of the trial’s investigators. “However, the signal is strong.”

After infectious disease and cancer, rare diseases are likely to be the next focus. Here, companies hope to take advantage of mRNA’s unique ability to issue genetic instructions.

In December, Vertex announced the launch of a clinical trial of inhaled mRNA for cystic fibrosis. The vaccine will hopefully instruct the lung cells to make new copies of a missing or faulty, but crucial, protein.

“To be able to inhale mRNA, and then have your lungs encode the mRNA and then express the correct protein – that, to me, sounds like Star Trek,” says Associate Professor Timothy Mercer, director of the BASE mRNA facility at the University of Queensland.

Not every mRNA therapy will try to directly encode genetic information. Melbourne-based RAGE Biotech is working on a molecule that alters the splicing of mRNA as the body makes it, changing how genes are expressed.

“It’s not changing the gene,” says Christopher Wraight, the company’s director. “It’s just shifting a natural process in a healthy direction.”

The company hopes to use that technology to cut the number of inflammatory proteins in the lung, with the hope of treating lung disease. Clinical trials are planned in coming years.

Liam Mannix’s Examine newsletter explains and analyses science with a rigorous focus on the evidence. Sign up to get it each week.

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Original URL: https://www.smh.com.au/national/it-s-not-hype-covid-vaccine-technology-to-fight-another-deadly-virus-then-cancer-20230208-p5cisl.html