The first doses for the Moderna Covid-19 vaccine, which was approved in emergency situations in the United States nine months ago, will arrive on Australian shores starting September. In an era of record cases and rolling lockdowns, the second mRNA vaccine against coronavirus has been a welcome addition.
Australia's slow vaccine rollout is a testament to its notorious slowness. This has been caused by the failure to develop a vaccine candidate locally and changes to the age-group recommendations for AstraZeneca vaccine due to the link to blood clots.
The pace has been slowed by insufficient supplies of mRNA vaccinations, primarily the one jointly produced by Pfizer (and BioNTech) What is stopping Australia from producing its own doses of mRNA vaccines?
Small biotech sector
Dr Archa Fox is an expert in RNA (ribonucleic acids) at the University of Western Australia. She says that mRNA technology was originally tested for cancer treatment.
Moderna, BioNTech, and CureVac were founded about ten years ago. They basically tried to take the research idea of creating RNA, altering it, [and] delivering that into cells to provide some therapeutic benefit.
In the initial clinical trials, they discovered that there was a strong immune response.
They discovered that they might be able to use this immune response for vaccines.
In 2018, mRNA vaccines were hailed as a new era of vaccinology because of their high potency and ability for rapid development, low cost manufacturing and safe administration.
People line up outside the Covid-19 vaccination clinic, which is located in Bankstown, Sydney. On Friday, 882 Covid cases were reported in NSW. Photograph: Loren Elliott/Reuters
Fox claims that although the Covid vaccines for mRNA were quickly introduced to the market, the technology was in development for many years.
Moderna and BioNTech were the only ones. They weren't large companies, and they hadn't been able bring a drug on the market.
It is not surprising that no local production of mRNA Covid vaccinations has been possible.
Fox states that because our biotech industry is small, there wasn't much demand for something unproven.
Professor Trent Munro from the University of Queensland said that Australia's relative lack of biotechnology infrastructure is a factor. This is in contrast to countries like the US, Singapore, and South Korea. The complex pharmaceutical manufacturing infrastructure was very limited in Australia, except for CSL and a few smaller facilities.
Slower than the mark
The federal government launched an approach to market in May and invited bids from biotech companies interested in making mRNA vaccines at home. Last month, the government received proposals from several local players, including CSL Limited, Australia's sole onshore vaccine manufacturer.
The federal government invited bidders from biotech companies interested in manufacturing mRNA vaccinations onshore. This was only May.
Australian biotech company AstraZeneca has been producing local doses for the AstraZeneca vaccination, an adenovirus-based one. The candidate vaccine was found to be falsely positive for HIV CSL. This vaccine had been produced by the Australian biotech company AstraZeneca before the University of Queensland's vaccine trial was halted.
Lorna Meldrum is the vice-president for pandemic readiness at Seqirus CSLs vaccine division. She says that the company already has an mRNA program and human clinical trials will begin next year for influenza vaccines.
She says that the company is actively looking into mRNA manufacturing options.
She says that vaccine manufacturing capacity cannot be established overnight. It takes time, investment, and dedication.
Complex technology
Every cell in our bodies contains genetic material in the form DNA. This familiar form is a double-stranded Helix.
RNA is similar, but it is single-stranded. RNA is used by viruses as their genetic code. In many organisms, including humans, it is made by enzymes which unzip the double Helix of DNA and make a copy of one strand.
There are many types of RNA. Messenger RNA mRNA is a particular type of RNA that is found in all cells. It serves as the blueprint for creating proteins and is present in all cells.
The mRNA Covid vaccines have a synthetic sequence of mRNA. This blueprint tells our cells to make the Covid-19 virus' spike protein. This spike protein is what the virus uses to infect our cells during a Covid infection. It then triggers an immune response.
Scott Morrison, Australian prime minister, at the AstraZeneca labs in Macquarie Park (Sydney). Photograph: Nick Moir/EPA
It is possible to modify the blueprint to encode for other proteins, so it's not limited to Covid.
The Covid mRNA vaccinations are made in three steps. First, bacteria grows DNA strands within small molecules called plasmids. These are then purified and transformed to mRNA using enzymes. The last step is to cover the mRNA with a layer of cholesterol, a class of substances that fats are.
Professor Robert Booy of University of Sydney says that the final step of the process is the most difficult. This is crucial because mRNA can be rapidly destroyed if it is not protected and encapsulated.
Max Rossetto is the head of business development for Luina Bio. Luina Bio, a Brisbane-based pharmaceutical company, is one of the companies that have submitted a proposal for domestic manufacturing to the federal government.
Rossetto states that the trick to mRNA vaccines is not making the mRNA but making the lipid capsule around the virus. Moderna and Pfizer were able to achieve this success by using this technology.
Dr Wayne Finlayson is the chief executive officer of Servatus. He is a Sunshine Coast drug manufacturer and developer who has submitted a bid to the government. Finlayson says that only two companies currently make the lipid nanoparticle capsules.
He says that even Moderna and Pfizer have outsourced this technology. If no one wanted it, we would have to create it in Australia.
License IP
The government's approach to market called for mRNA manufacturing plans that could be fully operational on a large scale at a population level in 12 months to three years.
Booy says there are many factors that could lead to manufacturing delays, such as supply chain issues and licensing issues. Pfizer stated that its Covid vaccine uses more than 280 materials from 19 countries.
Finlayson believes that licensing the Covid vaccines from Moderna and Pfizer is the fastest way to scale up manufacturing. We could probably do it in 18 months if we had the money and were told to.
Munro is more optimistic, though he has a similar estimate. Even if Moderna or Pfizer were to partner with someone, I believe it would take 18 months to two years, under the best of conditions.
More than nine months after being approved in emergency in the United States, the first doses for the Moderna Covid-19 vaccine are due to arrive in Australia in September. Photograph: Hollandse Hoogte/REX/Shutterstock
BioNTech had announced in May that it would establish a regional vaccine manufacturing plant in Singapore. It also signed a licensing agreement with Fosun Pharma, China to allow domestic production of 1bn doses its Covid vaccine.
They are unlikely to set up shop in Australia anytime soon. Guardian Australia was informed by Pfizer that it is focusing on global manufacturing in Europe and the US to supply Covid-19 vaccine to Australia.
Pfizer will assess all manufacturing opportunities once the pandemic supply phase has ended.
Christian Porter, the Australian science minister, stated last week that there were not many chances for either Pfizer nor Moderna to license their IP to a local company. He also said that talks were ongoing with Moderna, which Guardian Australia has reached out to for comment on the possibility of the company setting up a domestic manufacturing facility.
Fox said: It would take longer if we were to develop our own mRNA vaccination. This is because clinical trials are required. Monash University has begun trials of a locally produced mRNA vaccination. These trials will begin later in the year.
Investments are crucial
Finlayson believes mRNA vaccines will be a game-changer because they can be quickly updated for Covid variants. You only need to know the sequence of virus to be able to begin manufacturing within six weeks.
Booy states that Australia is a major exporter of flu vaccines worldwide and may eventually become an exporter for Covid vaccines.
Under the best circumstances, it can take 18 months to two years. Prof Trent Munro
Is it worth the cost of RNA technology when there is a long wait before a Covid vaccine can be manufactured locally?
Professor John Shine, president of the Australian Academy of Science, stated this week that onshore RNA capabilities are critical for vaccine development as well as for addressing problems like assessing biosecurity threats and supporting climate adaptation in agriculture.
Fox states: Fox believes it is possible that, just like annual flu shots, we will only need to continue receiving Covid-19 shots for an extended period of time. You could argue that the Modernas or Pfizer BioNTechs in other parts of the world should produce them and then send them to us.
There is still a case, even for Covid [vaccines], that this should be set up.
Individualised treatments for cancer, autoimmune diseases, and non-viral pathogens like malaria will all be common uses of mRNA vaccinations.
This disruptive technology is set to revolutionize medical products.
