FIn September, more than nine months after its approval for emergency use in the United States, the first doses of the Modern Covid-19 vaccine will reach Australian shores. The second mRNA (messenger ribonucleic acid) vaccine against coronavirus is a welcome blessing amid a period of continuous lockdowns and record numbers of cases.
But the notoriously slow launch of a vaccine in Australia has been marred by the failure of a locally developed candidate vaccine, as well as changes in the age group recommendations for the AstraZeneca vaccine as a result of its link to rare blood clots but .
But above all, the insufficient supply of mRNA vaccines, mainly the vaccine produced jointly by Pfizer and the German company BioNTech, has certainly slowed the pace. What prevents Australia from making its own doses?
Small biotech sector
Dr Archa Fox, an RNA (ribonucleic acid) expert at the University of Western Australia, says the mRNA technology was initially tested for cancer treatments.
“About 10 years ago, companies like Moderna, BioNTech and CureVac started, basically trying to take this research idea of making RNA, modifying it. [and] distributing it in cells to provide some therapeutic benefit, ”she says.
“What they found in the first clinical trials was that there was a strong immune response.
“In fact, they realized that maybe they could use that immune response for vaccines.”
In 2018, mRNA vaccines were announced as “A new era in vaccinology” for its “high power, rapid development capacity and potential for low-cost manufacturing and safe administration.”
Although Covid’s two mRNA vaccines were quickly brought to market, the technology has been in development for years, Fox says.
“There really only existed Moderna and BioNTech. They were not large companies and they had not yet been able to bring a drug to the market ”.
In some respects, it is not surprising that there has been no local production of Covid mRNA vaccines to date.
“Since our biotech sector is quite small to begin with, there was no commercial appetite to jump into something that was not yet proven at the time,” says Fox.
Professor Trent Munro of the University of Queensland says that Australia’s relative lack of biotech infrastructure, compared to countries like the United States, Singapore and South Korea, is also a factor. “Complex pharmaceutical manufacturing infrastructure – we are very limited here, outside of CSL and some small facilities.”
Slow down the brand
In May alone, the federal government announced a go-to-market approach, soliciting bids from biotech companies interested in making mRNA vaccines on land. The government received proposals last month from several local players, including leading CSL Limited, which is currently Australia’s only onshore vaccine manufacturer.
The Australian biotech company has been producing local doses of the AstraZeneca vaccine, which is an adenovirus-based vaccine. Before a University of Queensland vaccine trial was stopped (the candidate vaccine gave false positive HIV test results), the Commonwealth had also contracted with CSL to supply 51 million doses of that vaccine.
Lorna Meldrum, vice president of pandemic preparedness for Seqirus, CSL’s vaccine division, says the company already has an mRNA research program, with human clinical trials for influenza vaccines beginning next year.
“We are actively exploring mRNA manufacturing options for the company,” he says.
Vaccine manufacturing capacity “cannot be configured overnight,” he says. “It takes time and investment.”
Each of the cells in our body contains genetic material in the form of DNA, with its familiar double-stranded helix shape.
RNA is similar, but is instead single-stranded – viruses use it as their genetic code, while in many organisms, including humans, it is made by enzymes that decompress the DNA double helix and take a copy of one of the strands .
There are different types of RNA. One particular type, messenger RNA, mRNA for short, plays a crucial role as a blueprint for protein production and is naturally present in all of our cells.
Covid mRNA vaccines contain a synthetic mRNA sequence, a blueprint, that tells the cells of our bodies to produce the spike protein of the Covid-19 virus. The presence of that spike protein, which during a real Covid infection is used by the virus to infect our cells, triggers an immune response.
The blueprint can be easily modified to encode other proteins, which means it is not limited to just treating Covid.
Simply put, Covid mRNA vaccines are made in a three-step process: As a first step, bacteria grow strands of DNA into small molecules known as plasmids, which are then purified and converted to mRNA by enzymes. The last step is to coat the mRNA with a layer of lipid, a class of substances to which fats belong.
The final step in the process is the most challenging, says Professor Robert Booy of the University of Sydney. “It is incredibly important because mRNA breaks down quickly unless it is protected and encapsulated.”
Max Rossetto, Luina Bio’s head of business development, agrees. Luina Bio is a Brisbane-based pharmaceutical manufacturer among companies that have submitted a national manufacturing proposal to the federal government.
“In mRNA vaccines, the trick is not so much making the mRNA as the lipid capsule that surrounds it,” says Rossetto. “Finding this technology is what made Pfizer and Moderna so successful.”
Dr. Wayne Finlayson, CEO of Servatus, a Sunshine Coast drug developer and manufacturer that has also submitted a government bid, says that to his knowledge, only two companies in the world currently produce the lipid nanoparticle capsules.
“Even Moderna and Pfizer outsource that,” he says. “We would have to develop that technology in Australia if no one is going to give it to us.”
Intellectual property licenses
In the government’s market approach, it called for mRNA manufacturing proposals that would be fully operational on a population scale in a time period of between 12 months and three years.
Booy says that several factors can lead to manufacturing delays, including raw material supply chain issues and vaccine licensing issues. (In a statement, Pfizer says its Covid vaccine “involves the use of more than 280 materials from 86 suppliers in 19 different countries.”)
Finlayson believes that the fastest path to large-scale manufacturing would be to license the Covid vaccines from Pfizer and Moderna. “If we had the money and they told us to do it, we could do it in probably 18 months.”
Munro has a similar estimate, but is less optimistic: “Even if we did have Pfizer or Moderna come in and partner with someone, my view is that it’s 18 months to two years in the best of circumstances.”
In May, BioNTech announced that it would establish a regional vaccine manufacturing plant in Singapore. That same month, it signed a licensing agreement with the Chinese firm Fosun Pharma to allow the domestic production of 1 billion doses of its Covid vaccine.
They are unlikely to settle in Australia in the near future. In a statement to Guardian Australia, Pfizer says it is “focusing on global manufacturing at our manufacturing centers in Europe and the US for the pandemic supply of our Covid-19 vaccine for Australia”.
“Once the pandemic supply phase is complete and we enter a regular supply phase, Pfizer will evaluate all available additional manufacturing opportunities.”
Australian Science Minister Christian Porter said last week the chances of Pfizer or Moderna licensing IP to a local manufacturer were “remote,” and that discussions continued with Moderna, whom Guardian Australia has contacted for comment, about the company establishing its own plant. manufacturing in the country.
Fox says, “If we were to go down the road of developing our own mRNA vaccine … then it looks more like that three-year period.” The process would be longer due to the need for clinical trials. Trials of a locally produced mRNA vaccine, developed by Monash University, are scheduled to start later this year.
Finlayson says mRNA vaccines are “a game changer” because they can be quickly updated, even for Covid variants. “All you have to do is know the sequence of the virus and, in six weeks, you can basically be ready to start manufacturing.”
Australia is a global exporter of flu vaccines and could eventually become an exporter of Covid vaccines as well, says Booy.
But given the long span of time until a locally manufactured Covid mRNA vaccine is it worth the investment in RNA technology?
Professor John Shine, President of the Australian Academy of Sciences, wrote this week that the capacity of RNA in land “is essential not only for the development of vaccines, but also to address problems such as the assessment of new biosecurity threats and support for adaptation to climate change in agriculture.”
Fox says: “It’s possible, just like with annual flu shots, that we have to get annual Covid-19 vaccinations for a long time. I suppose you could argue: well, let Modernas and Pfizer-BioNTech in other parts of the world produce them and then ship them to us.
“I think there is still a discussion, even for Covid [vaccines], to install here “.
The broader uses of mRNA vaccines will likely include individualized cancer treatments and treatments for autoimmune diseases and non-viral pathogens such as malaria.
“This is really a disruptive technology that is going to change all kinds of medical products.”
George is Digismak’s reported cum editor with 13 years of experience in Journalism