Australian mRNA vaccines?

Yesterday the Victorian Government announced a $50 million investment to set up a facility to develop and manufacture mRNA vaccines in Australia. Monash University’s experts will work with the Victorian Government, the University of Melbourne and The Doherty Institute to establish and scale mRNA vaccine manufacturing.

“That’s just the start,” says Associate Professor Archa Fox, a molecular biologist and mRNA expert at the University of Western Australia.

Although it’s early days, the Victorian Government announcement has been welcomed with enthusiasm by the Australian scientific community.

“Great development… It’s time for all States and Territories to engage – we need to go further and establish a federated, collaborative and flexible network of R&D/manufacturing/clinical trials capability and capacity,” tweeted Professor Paul Young, a molecular virologist and research leader of the molecular clamp vaccine developed at the University of Queensland.

“We have many scientists in Australia who are very excited to develop new intellectual property around improving the design of the mRNAs,” says Fox. “There is a lot of opportunities for Australian research and biotech to innovate with this.”

Last year, Monash University researchers collaborated with The Doherty Institute and, led by Professor Colin Pouton, developed Australia’s first COVID-19 mRNA vaccine candidates. But the production of Australian-designed mRNA vaccines will still take a long time because these candidates are yet to go through clinical trials.

“It will take a while to get this going, but we’ll almost certainly need next-gen vaccines to deal with mutant strains and mRNA looks to be the ‘fast and flexible’ way to go,” tweeted immunologist and Nobel laureate Professor Peter Doherty.” Pfizer, Moderna-style vaccines could soon be made in Melbourne.”

“We are looking to the future, two or three years down the track, perhaps for boosters,” Fox says.

In the past months, Australia’s leading scientists have urged the government to invest in updated vaccine manufacturing capability and begin producing mRNA vaccines, such as Pfizer’s, onshore. Without this ability, Australia remains vulnerable to supply limitations.

Currently, the Australian government has ordered 40 million Pfizer doses, enough to cover almost the entire population. If we are happy to wait for when those come through – possibly towards the end of the year – then there would be no need to produce them here.

“However, that is a very temporary solution to what will be an ongoing problem,” says Fox. She says we should be thinking beyond the rollout of the current vaccines because it is likely that we will need annual boosters to cover emerging variants, or simply because our immunity fades with time.

“So given that the mRNA vaccines are the most effective and don’t have the blood-clot issues that the AstraZeneca has, we think that this is something we ought to do,” she says.

What it takes to set up a facility adapted to manufacture the Pfizer or Moderna vaccine in Australia is a substantial investment. We’d have to buy the necessary equipment and get our scientists trained.

“It actually doesn’t require as large a footprint as some of the other types of biomanufacturing,” says Fox. She explains that with mRNA vaccines there is no need to grow cells in large volumes. Instead, it is a much simpler synthetic process.

To synthesise mRNA, scientists insert the sequence corresponding to the mRNA into a plasmid, a small DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate itself. This plasmid is put into a reactor where an enzymatic reaction triggers the synthesis of the mRNA. This is purified and encapsulated in a lipid nanoparticle.

All these steps can take place in pods, little cleanrooms about the size of a shipping container. “So you can scale up by ordering more of these pods as you need,” says Fox.

The final step is to put the vaccine into the vials, which doesn’t have to happen in the same site. “It’s called ‘fill and finish’, and we already have that capacity,” says Fox.

While there was understandable scepticism about this previously unproven technology at the beginning of the pandemic, hundreds of millions of people have been injected with these vaccines to date. They are effective and they are safe, says Fox. “COVID has been the breakthrough that this technology needed, and it is clear that this is the most exciting area in biotech now.”

There are many other viruses we need to develop vaccines against, some of which are especially problematic for Australia, says Fox. One is the human T-lymphotropic virus (HTLV), endemic among indigenous communities. Ross River virus, a mosquito-borne alphavirus endemic to Australia, Papua New Guinea and other islands in the South Pacific, is another.

But beyond infectious diseases, huge areas of development for mRNA technology are cancer and customisable medicine.

Fox says substantial investments in this area of research would prompt advances in many areas of medicine. “We have many mRNA experts in Australia who want to help in this research. And we think that it will actually trigger a bit of a biotech boom,” she says. “We really don’t want to be left behind.”