Why can’t Australia make mRNA vaccines? Because we don’t make enough ‘deep technology’ companies

Posted on September 14, 2021 by particularkev

Julian Waters-Lynch, RMIT UniversityCaught out by its strategy to bet on COVID-19 vaccines that could be made in Australia, the federal government is now scrambling to manufacture mRNA vaccines locally.

Its “approach to market” strategy has effectively asked companies how much government money they need to do so. But even with subsidies, this plan will take years.

So why can’t Australia make the mRNA vaccines?

That’s not actually the right question to ask. The crucial issue is why Australia hasn’t been producing the type of companies that can make mRNA vaccines. Why don’t we produce more start-ups like BioNTech or Moderna – the two companies that developed and brought the mRNA vaccines to market?

Answering this question is important not just to vaccines but to the whole range of “deep technologies” that will shape economic development and sustainability in the 21st century.

What is deep technology

Technology is generally defined as the application of new knowledge for practical purposes. Deep technology is slightly different. It refers to the type of organisation required to bring certain types of technological innovation to fruition.

It is more accurate to talk about deep technology ventures. BioNTech and Moderna are two such examples. Both are relatively young companies — BioNTech was founded in Germany in 2008, Moderna in the US in 2010 — that have brought to market a technological solution underpinned by substantive advances in scientific research, engineering and design.

Deep-tech ventures span advanced materials, artificial intelligence, biotechnology, blockchains, robotics and quantum computing. A few are now household names, such as Tesla and SpaceX, but most fly under the radar of public awareness, as Moderna and BioNTech did before the pandemic.

They include synthetic biology companies such as the Ginkgo Bioworks and Zymergen, which can program organisms to create completely new biologically based materials for use in manufacturing. These “biofoundries” can produce everything from biodegradable plastics, new protein-based foods to probiotic microorganims that improve human health.

There are advanced engineering companies such as Carbon Engineering and Climeworks, working on ways to suck carbon dioxide from the air to use for industrial purposes.

There are experimental energy companies such as Commonwealth Fusion Systems and Helion, which are working on making the holy grail of clean energy technology, nuclear fusion, a reality.

Australia’s problem with deep tech

Australia’s problem with deep technology ventures isn’t to do with the quality of our science and research. We produce, per capita, nearly twice as many scientific research papers as the OECD average.

We also have some great support structures, such as the CSIRO, the national research and science agency, and Cicada Innovations, the deep-tech venture incubator in Sydney.

The problem is our inability to take our scientists’ knowledge and turn it into innovative ventures. Other countries are much more successful at this. Britain, Germany and France, for example, all publish fewer research papers than Australia per capita but produce far more patent applications — a key indicator of potential research commercialisation. The US produces nine times as many per capita.

The ‘valley of death’

Australia’s primary challenges here are related to the culture of innovation and entrepreneurship and our current mechanisms for long-term venture funding.

Deep-tech ventures usually require longer time horizons to translate new scientific insights into commercially successful products. Few universities are set up to see this process through. Public funding mechanisms prioritise basic research leading to publications, not the entrepreneurial processes required to find a market fit for a new product or solution.

Nor are venture capital funds — the normal providers of seed funding — well placed to fund deep technology ventures. This is partly because the science itself can be difficult to understand. Also many funds prioritise ventures that can “exit” through an acquisition or public offering within 10 years.

The complex science and length of time needed to commercialise deep tech mean many good ideas die in the so-called “valley of death” — the gap between initial seed funding and sustainable revenue generated from product sales. This gap is filled in some countries by investments from sovereign wealth funds, more “mission” oriented government programs and even prizes. Australia has yet to emulate these solutions.

These issues help explain why Australia’s investment in R&D as a portion of GDP over the past decade has declined, from a peak of 2.3% in 2008 to 1.8% in 2019. That puts us below the OECD average (2.47% in 2019), well behind innovation leaders such as Israel (4.9%), South Korea (4.6%) and Taiwan (3.5%).

In 2020 only 12 Australian companies were listed among the world’s top 2,500 R&D leaders (as ranked by EU Industrial R&D Investment Scoreboard). This compares with Taiwan (88), South Korea (59) Switzerland (58), Canada (30) and Israel (22).

What can we do about it?

Australia’s future economic prosperity depends on our ability to translate scientific advances into innovation and entrepreneurship. Technological innovation is the only driver of economic growth over the long term. MIT professor Robert Solow won the 1987 Nobel Prize in Economics for his work demonstrating this point.

To correct our trajectory requires more “patient” capital. We are one of the world’s wealthiest nations on a per capita basis, but too much wealth is locked up in property ($8 trillion) and superannuation funds ($3.8 trillion) opting for “safer” investments.

If just 0.1% of superannuation assets were allocated to fund deep technology ventures, Australia would have a fund about as large as the nation’s entire current venture capital pool invested in the past financial year.

We also need leadership around a shared vision of the benefits of deep technology entrepreneurship. Not enough Australians recognise the importance of science and technology in driving both economic prosperity and addressing global challenges. Some are even suspicious that technology causes more problems than it solves.

But these ventures will be crucial to addressing pressing development and sustainability challenges, including climate change.

Tomorrow’s economy and society will be built with today’s scientific breakthroughs in deep technology ventures.

Julian Waters-Lynch, Lecturer Entrepreneurship, Innovation and Organisational Design, RMIT University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

What’s Australia’s first local Pfizer-style COVID vaccine? And when might it be in our arms? An mRNA expert explains

Posted on June 28, 2021 by particularkev

Archa Fox, The University of Western AustraliaAustralia has struggled to get enough Pfizer doses to meet Australians’ growing demand for COVID-19 vaccinations.

Australia has been producing doses of AstraZeneca since March, but this vaccine is no longer recommended for those aged under 60 because of the small but serious risk of clotting.

Now a research team at Monash University, led by Professor of Pharmaceutical Biology Colin Pouton, hopes to develop a new mRNA vaccine, which works by the same principles as the Pfizer vaccine, and could be manufactured locally.

So how would the vaccine work? What hurdles do the researchers need to overcome to make it a reality? And when could it become available?

It’s based on existing technology

Before COVID, the researchers were developing mRNA vaccines against a variety of viruses and diseases, and testing the technology in mice. After the pandemic hit, they pivoted their skills and technology and started work on an mRNA vaccine against COVID-19.

The vaccine is an mRNA vaccine, like the ones by Pfizer and Moderna. These vaccines prompt your body to produce the virus’ spike protein, to which your immune system makes antibodies against.

But the Monash mRNA vaccine is a little bit different, as it directs our cells to only make a small part of the spike protein, the “receptor binding domain”, which is the most important part allowing the virus to enter our cells.

The receptor binding domain, or tip of the spike protein, is also the part that’s quickly mutating to form the different variants of concern. Directly targeting this part makes sense to get the most variant-specific response.

How do mRNA vaccines work again?

MRNA vaccines work as instructions, telling our cells to make certain proteins. If these proteins are foreign to our bodies, our immune system will recognise them and mount an immune response. Over time, immune memory is developed, meaning when we encounter the virus, our immune system will clear it.

The researchers began modelling the vaccine off the original strain of the virus, first discovered in Wuhan. But they’ve since adjusted their sequence to model the shot off the Beta variant, first discovered in South Africa. This adjustment was made partly because the neutralising antibodies from patients infected with the Wuhan strain are least effective against the Beta variant.

Our current crop of approved COVID vaccines protect well against the Alpha variant, first found in the United Kingdom, and the Delta variant, first discovered in India. But because the Beta variant is good at evading immunity from vaccines, it’s more likely than most other variants to surge when vaccine protection begins to wane.

For these reasons, there’s a stronger clinical need for Beta variant vaccines.

This quick adjustment of the sequence demonstrates how flexible the mRNA technology is. It’s easy to change the sequence of the vaccine to adapt to new variants of the virus that have emerged, and might emerge in future. This ability to quickly change the sequence is similar for DNA vaccines like AstraZeneca, but harder for traditional and protein-based vaccines.

As with all other mRNA vaccines, the RNA will be broken down in the body over the course of a day or so. The vaccine doesn’t stay in your body over the long term. You gain immunity as your immune system learns how to respond to the short burst of proteins your body makes. When you get the second dose of mRNA vaccine, the immune memory is reinforced.

The group has tested this vaccine in mice, and says its results are really promising.

Based on these pre-clinical results, the Victorian government has given the project A$5 million. The money has come out of a A$50 million research fund earmarked to support local mRNA vaccine development.

The A$5 million will help pay for a manufacturer in Europe to make a sufficient amount of the mRNA for the phase 1 trials. This material will then be shipped via ultra-cold storage to Australia, and a local company is going to package the RNA into “lipid nanoparticles” which allows the mRNA to get into human cells.

What are the next steps?

Phase 1 trials to check the vaccine is safe in humans will begin in October or November this year, and will initially include 150 volunteers.

If the vaccine passes this trial, it will move to phase 2 and 3 trials which require tens of thousands of participants. The primary aim of these later stage trials will be to see if the vaccine can reduce the severity of COVID-19 disease, while also checking it’s still safe.

These later stage trials are quicker to complete if conducted in areas with (unfortunately) high community transmission. One reason we saw Pfizer and Moderna’s vaccines approved so quickly was because trials took place in countries where the virus was rampant. If and when this vaccine goes to phase 2 and 3 trials, Australia will hopefully not be in a situation with widespread transmission. So the team may need to involve international partners and recruit participants overseas.

However, there may also be alternative metrics to measure how well a vaccine is working. Researchers can look at study volunteers’ blood to see how many, and the type of, antibodies they’re producing. This could work as a proxy for measuring efficacy. But it’s not clear if Australia’s drug regulator, the Therapeutic Goods Administration, would approve the vaccine without the traditional exposure model.

The team will also compare their mRNA vaccine directly with Pfizer, in a side-by-side comparison, to see how stable it is and how well it elicits antibodies against the virus.

So when can we get it into our arms? It’s uncertain how long the full suite of trials will take, but probably not for a couple of years. It’s possible the vaccine will not make it past phase 1 or 2 trials, although with the similarity in methodology to the Pfizer and Moderna vaccines, both of which are safe, this is less likely.

Why we need Australian-made vaccines

This is an important step in developing Australia’s sovereign capacity for mRNA vaccine production, and for the newly developing Australian RNA biotechnology sector as a whole. It’s likely we’ll need booster shots for some years to come, so we need to develop local manufacturing capability.

I sincerely hope it’s successful, but even if it’s not, it’s creating a pipeline for onshore mRNA vaccine development.

What’s more, mRNA vaccines are the new gold standard and the next generation vaccine technology. It’s likely we’ll see more pandemics and novel viruses in future, so that adds to the argument for having local mRNA vaccine capacity.

We don’t know how much the federal government paid for the Pfizer and Moderna vaccines, but it’s likely to have been much more costly than making it here. If we can make it ourselves more cheaply, we’re at a real advantage.

Archa Fox, Associate Professor and ARC Future Fellow, The University of Western Australia

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Research now backs routinely offering pregnant women the mRNA COVID-19 vaccine

Posted on June 27, 2021 by particularkev

Michelle Wise, University of AucklandNew Zealand and Australia will now routinely offer the Pfizer COVID-19 vaccine to women at any stage of pregnancy, following an update of vaccination advice.

This comes as research suggests the risk of severe outcomes from infection is significantly higher for pregnant women compared to the general population. At the same time, data from pregnant women who have already been vaccinated around the world have shown no safety concerns associated with COVID-19 vaccines.

Vaccination during pregnancy may also protect the baby. Research has identified antibodies in cord blood and breast milk, suggesting temporary protection (passive immunity) for babies before and after birth.

This is similar to influenza and whooping cough vaccines given during pregnancy to protect pēpi. There are no safety concerns for breastfeeding women receiving a COVID-19 vaccine, and women trying to become pregnant do not need to delay vaccination or avoid becoming pregnant after vaccination.

Prioritising pregnant women

When the New Zealand government announced its vaccine rollout plan in March, pregnant women were designated as a priority in the third group, which includes 1.7 million people who are at higher risk if they catch COVID-19.

This decision reflected the available information at the time from international research showing pregnant women with COVID-19 were more likely to be hospitalised and admitted to intensive care, compared to the rest of the population.

Breastfeeding baby — Vaccinating women during pregnancy is likely to provide temporary protection for babies as well.
Shutterstock/Natalia Deriabina

The higher risk of hospitalisation is similar to other priority populations, including people aged 65 and over, and those with underlying health conditions or disabilities. People in these groups are also more likely to get very sick if they get COVID-19.

New Zealand’s decision was part of a principled strategy that aims to provide fair and equitable care based on scientific evidence, acknowledging research that places pregnant women in a high-risk group if they were to be infected.

Changing advice to pregnant women

Initial advice from the Immunisation Advisory Centre was that women could receive the vaccine at any time during pregnancy, but for those at low risk of exposure, they recommended delaying vaccination until after birth.

The Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) published similar early advice, stating that women could choose to have the vaccine at any stage of pregnancy, particularly if they were in a high-risk population. But they did not recommend routine universal vaccination if levels of community transmission were low.

So what has changed since March? It became urgent to review the early advice as local vaccination centres have started vaccinating people in the third group of the rollout. Also, travel bubbles with Australia and the Cook Islands meant people were possibly more exposed to transmission.

The early advice in New Zealand and Australia was also diverging from other countries, such as Canada. And more research is coming out about the risks of COVID-19 infection in pregnancy, while international experience with mRNA-based vaccines (such as Pfizer-BioNTech) in pregnant women is growing.

Pregnant women were not included in the original clinical trials to test COVID-19 vaccines for safety. But there is no evidence of any harm associated with the vaccine during pregnancy.

Vaccine trials in the US are now actively recruiting pregnant women. We can expect research results by the end of this year. In the meantime, we can be reassured by registries, which are studies that track women who have had the vaccine during pregnancy and have given consent to have information collected about them and their babies.

Researchers in the US found women who received the vaccine during pregnancy had outcomes similar to background rates for the mother (regarding rates of miscarriage, diabetes, high blood pressure) and the baby.

Side effects from receiving the vaccine were also the same in pregnant and non-pregnant women, and it is safe to take paracetamol as needed to manage these.

Other countries, including the UK, have published decision aids to help with this important decision. I encourage professional groups to create one for New Zealand women planning or going through pregnancy.

Research supports routinely offering the vaccine to pregnant women, and it is up to individuals to decide whether to receive it or not, as part of a shared decision-making process with their midwife or doctor.

Michelle Wise, Senior Lecturer, Department of Obstetrics and Gynaecology, University of Auckland

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Can the Pfizer or Moderna mRNA vaccines affect my genetic code?

Posted on June 26, 2021 by particularkev

Archa Fox, The University of Western Australia; Jen Martin, The University of Melbourne, and Traude Beilharz, Monash UniversityThe Pfizer and Moderna vaccines are set to become the mainstay of Australia’s COVID-19 vaccine rollout as the year progresses, according to the latest government projections released this week.

From September, up to an average 1.3m doses of the Pfizer vaccine plus another 125,000 doses of the yet-to-be approved Moderna vaccine are expected to be available per week. These figures are set to rise from October, as use of the AstraZeneca vaccine drops.

Both the Pfizer and Moderna vaccines are mRNA vaccines, which contain tiny fragments of the genetic material known as “messenger ribonucleic acid”. And if social media is anything to go by, some people are concerned these vaccines can affect their genetic code.

Here’s why the chances of that happening are next to zero and some pointers to how the myth came about.

Remind me, how do mRNA vaccines work?

The technology used in the Pfizer and Moderna vaccines is a way of giving your cells temporary instructions to make the coronavirus spike protein. This protein is found on the surface of SARS-CoV-2, the virus that causes COVID-19. The vaccines teach your immune system to protect you if you ever encounter the virus.

The mRNA in the vaccine is taken up by the cells in your body, ending up in the liquid inside each cell known as the cytoplasm. Our cells naturally make thousands of our own mRNAs all the time (to code for a range of other proteins). So the vaccine mRNA is just another one. Once the vaccine mRNA is in the cytoplasm it’s used to make the SARS-CoV-2 spike protein.

The vaccine mRNA is short-lived and is rapidly broken down after it’s done its job, as happens with all your other mRNA.

Typical mammalian cell, showing different parts, such as nucleus and cytoplasm — Vaccine mRNA is in the cytoplasm and once it’s done its job, it’s broken down.
www.shutterstock.com

Here’s why the mRNA can’t insert into your genetic code

Your genetic code is made up of a different, but related, molecule to the vaccine mRNA, known as DNA, or deoxyribonucleic acid. And mRNA can’t insert itself into your DNA for two reasons.

One, both molecules have a different chemistry. If mRNAs could routinely insert themselves into your DNA at random, this would play havoc with how you produce proteins. It would also scramble your genome, which is passed on to future cells and generations. Life forms that do this would not survive. That’s why life has evolved for this not to happen.

The second reason is vaccine mRNA and DNA are in two different parts of the cell. Our DNA stays in the nucleus. But vaccine mRNA goes straight to the cytoplasm, never entering the nucleus. There are no transporter molecules we know of that carry mRNA into the nucleus.

But aren’t there some exceptions?

There are some extremely rare exceptions. One is where genetic elements, known as retro-transposons, hijack cellular mRNA, convert it into DNA and insert that DNA back into your genetic material.

This has occurred sporadically throughout evolution, producing some ancient copies of mRNAs scattered throughout our genome, to form so-called pseudogenes.

Some retroviruses, such as HIV, also insert their RNA into our DNA, using similar methods to retro-transposons.

However, there is a vanishingly small chance of a naturally occurring retro-transposon becoming active in a cell that has just received a mRNA vaccine. There’s also a vanishingly small chance of being infected with HIV at precisely the same time as receiving the mRNA vaccine.

Blood sample labelled with HIV - Test — There’s a vanishingly small chance of being infected with HIV at precisely the same time as having an mRNA vaccine.
from www.shutterstock.com

Even if a retro-transposon were to become active or a virus such as HIV were present, the chances of it finding the COVID vaccine mRNA, among the tens of thousands of natural mRNAs, is extremely unlikely. That’s because vaccine mRNA is degraded within several hours of entering the body.

Even if vaccine mRNA did become a pseudogene, it would not produce the SARS-CoV-2 virus, but just one of the viral products, the harmless spike protein.

How do we actually know this?

We know of no studies looking for vaccine mRNA in the DNA of people who have been vaccinated. There is no scientific basis on which to suspect this insertion has happened.

However, if these studies were to be carried out, they should be relatively straightforward. That’s because we can now sequence DNA in single cells.

But in reality, it will be very hard to ever satisfy a naysayer who is convinced this genome insertion happens; they can always argue scientists need to look deeper, harder, in different people and in different cells. At some point this argument will need to be laid to rest.

So how did this myth come about?

One study reported evidence for coronavirus RNA integrating into the human genome in cells grown in the lab that had been infected with SARS-CoV-2.

However, that paper did not look at the mRNA vaccine, lacked critical controls and has since been discredited.

These types of studies also need to be seen in context of the public’s wariness of genetic technology more broadly. This includes the public’s concerns about genetically modified organisms (GMOs), for instance, over the past 20 years or so.

But GMOs are different to the mRNA technology used to make COVID vaccines.
Unlike GMOs, which are produced by inserting DNA into the genome, vaccine mRNA will not be in our genes or passed to the next generation. It’s broken down very quickly.

In reality, mRNA technology has all sorts of applications, beyond vaccines, including biosecurity and sustainable agriculture. So it would be a pity for these efforts to be held back by misinformation.

Archa Fox, Associate Professor and ARC Future Fellow, The University of Western Australia; Jen Martin, Leader, Science Communication Teaching Program, The University of Melbourne, and Traude Beilharz, Assoc Professor ARC Future Fellow, Biochemistry & Molecular Biology, Monash Biomedicine Discovery Institute, Monash University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

The world is hungry for mRNA COVID vaccines like Pfizer’s. But we’re short of vital components

Posted on April 29, 2021 by particularkev

Archa Fox, The University of Western Australia and Pall Thordarson, UNSWGiven the AstraZeneca COVID-19 vaccine is no longer recommended for under-50s following news of very rare blood clots, Australia is looking to other vaccines to plug the gap.

Pfizer’s mRNA vaccine will become the mainstay of the rollout, with 40 million doses expected to arrive before year’s end.

But Australia isn’t the only country eager to get its hand on this vaccine.

Skyrocketing demand coupled with shortages of vital components is leading to bottlenecks in the supply chain of this and other mRNA vaccines, delaying vaccine supplies.

The Victorian government also announced last week it would provide A$50 million to set up local manufacturing of mRNA vaccines in Australia. It’s feasible supply chain issues could also impact local manufacturing of mRNA vaccines.

So what are the missing supplies for making mRNA vaccines?

The shortages slowing mRNA vaccine production

1. mRNA manufacturing and capping

Manufacturing mRNA vaccines is kind of like making a car, with an assembly line and many steps. Each step needs to lead to the next and flow smoothly to make the final product.

COVID mRNA vaccine manufacturing starts with making the “messenger RNA”, the instructions that tell our cells to make the coronavirus’ spike proteins. The mRNA is produced in reactor vessels, where protein enzymes track along a DNA template and copy that DNA sequence into RNA form.

The first shortage is in sterile, single-use plastic bags which sit inside the metal reactor vessels used for making the mRNA, almost like a bin liner. Several suppliers of these plastic liners are ramping up production so it’s anticipated this shortage won’t last too long.

The second main shortage relates to “capping” the mRNA at one end. Capping involves adding a chemical molecule to the mRNA which stops the mRNA breaking down too quickly and helps our cells use the mRNA to make protein. Early on during the worldwide upscaling of mRNA manufacturing, rumours abounded that the enzymes and raw materials to make the mRNA cap were running short, given related enzymes used for COVID tests were also in short supply.

However, while only a few players dominate the field, this doesn’t seem to be a bottleneck now. But it does still remain one of the most costly parts of the mRNA production process.

2. Lipids in nanoparticles

The main bottleneck right now is the supply of some of the lipids making the nanoparticles that protect the mRNA and deliver it into our cells.

One lipid in particular, a so-called “cationic lipid”, wraps around the mRNA and then releases it inside the cell. Several chemical synthesis steps are required to make these cationic lipids, and prior to COVID only a handful of manufacturers worldwide were making these, and only on a fairly small scale.

Upscaling this production of cationic lipids has been even harder than setting up the mRNA production. Currently, four companies — Croda/Avanti, CordenPharma, Evonik and Merck — are the main manufacturers of these lipids.

As an indication of how serious this shortfall in lipids is, in December 2020 former US President Donald Trump invoked the Defense Production Act to assist Pfizer in accessing more lipids.

Why do we have these shortages?

The reasons for these shortages are complex. In most cases, demand has outstripped supply. In some cases, some countries or companies have been stockpiling some of these components. “Operation Warp Speed”, initiated by the Trump administration to speed up COVID vaccine development, used its financial clout throughout 2020 to buy up and secure many vaccine components including vials and lipids. This has put the vaccine manufacturers based in the United States in a good position, including Moderna and several Pfizer sites.

For some materials, the reason for the shortfall is simply that they’re hard to make. The bespoke cationic lipids are chemically synthesised in ten steps that all have to performed under strict quality control. Even if the equipment is ready, setting up such a manufacturing process takes months.

How could these shortages impact future mRNA manufacturing in Australia?

When Victoria’s new mRNA manufacturing facility comes online, hopefully in the next 12-24 months, some of these global shortages may still be plaguing the worldwide supply chains. This shouldn’t stop our efforts on that front as raw material supplies are rapidly increasing.

Australia should also do more manufacturing of small molecule active pharmaceutical ingredients, that is, the biologically active component in each drug, including lipids and other building blocks of mRNA. Australia imports over 90% of its drugs from overseas. Making active pharmaceutical ingredients is important, not just for COVID vaccines but more generally.

Australia nearly ran out of some essential drugs, like ventolin, in the early days of the COVID-19 crisis. This was due to both Australians’ panic buying, as well as COVID-hit Chinese factories slowing down their manufacturing, leading to a lack of access to these ingredients for our most commonly used drugs. The added benefits of locally based manufacturing of active pharmaceutical ingredients is we’d be part of the solution when components are in short supply in future.

Australia also has a very strong research community in mRNA and nanomedicine. There are several world-leading groups working on creating better lipid nanoparticles for the delivery of mRNA and other medical products.

Having access to local manufacturing capability of active pharmaceutical ingredients would therefore transform the ability of Australian researchers to lead the way in developing the next blockbuster medical technology based on mRNA or nanoparticle delivery.

Archa Fox, Associate Professor and ARC Future Fellow, The University of Western Australia and Pall Thordarson, Professor, Chemistry, UNSW

This article is republished from The Conversation under a Creative Commons license. Read the original article.

How mRNA Vaccines Work

Posted on April 25, 2021 by particularkev

3 mRNA vaccines researchers are working on (that aren’t COVID)

Posted on April 15, 2021 by particularkev

Archa Fox, The University of Western Australia and Damian Purcell, The Peter Doherty Institute for Infection and ImmunityThe world’s first mRNA vaccines — the COVID-19 vaccines from Pfizer/BioNTech and Moderna — have made it in record time from the laboratory, through successful clinical trials, regulatory approval and into people’s arms.

The high efficiency of protection against severe disease, the safety seen in clinical trials and the speed with which the vaccines were designed are set to transform how we develop vaccines in the future.

Once researchers have set up the mRNA manufacturing technology, they can potentially produce mRNA against any target. Manufacturing mRNA vaccines also does not need living cells, making them easier to produce than some other vaccines.

So mRNA vaccines could potentially be used to prevent a range of diseases, not just COVID-19.

Remind me again, what’s mRNA?

Messenger ribonucleic acid (or mRNA for short) is a type of genetic material that tells your body how to make proteins. The two mRNA vaccines for SARS-CoV-2, the coronavirus that causes COVID-19, deliver fragments of this mRNA into your cells.

Once inside, your body uses instructions in the mRNA to make SARS-CoV-2 spike proteins. So when you encounter the virus’ spike proteins again, your body’s immune system will already have a head start in how to handle it.

So after COVID-19, which mRNA vaccines are researchers working on next? Here are three worth knowing about.

1. Flu vaccine

Currently, we need to formulate new versions of the flu vaccine each year to protect us from the strains the World Health Organization (WHO) predicts will be circulating in flu season. This is a constant race to monitor how the virus evolves and how it spreads in real time.

Moderna is already turning its attention to an mRNA vaccine against seasonal influenza. This would target the four seasonal strains of the virus the WHO predicts will be circulating.

But the holy grail is a universal flu vaccine. This would protect against all strains of the virus (not just what the WHO predicts) and so wouldn’t need to be updated each year. The same researchers who pioneered mRNA vaccines are also working on a universal flu vaccine.

The researchers used the vast amounts of data on the influenza genome to find the mRNA code for the most “highly conserved” structures of the virus. This is the mRNA least likely to mutate and lead to structural or functional changes in viral proteins.

They then prepared a mixture of mRNAs to express four different viral proteins. These included one on the stalk-like structure on the outside of the flu virus, two on the surface, and one hidden inside the virus particle.

Studies in mice show this experimental vaccine is remarkably potent against diverse and difficult-to-target strains of influenza. This is a strong contender as a universal flu vaccine.

2. Malaria vaccine

Malaria arises through infection with the single-celled parasite Plasmodium falciparum, delivered when mosquitoes bite. There is no vaccine for it.

However, US researchers working with pharmaceutical company GSK have filed a patent for an mRNA vaccine against malaria.

The mRNA in the vaccine codes for a parasite protein called PMIF. By teaching our bodies to target this protein, the aim is to train the immune system to eradicate the parasite.

There have been promising results of the experimental vaccine in mice and early-stage human trials are being planned in the UK.

This malaria mRNA vaccine is an example of a self-amplifying mRNA vaccine. This means very small amounts of mRNA need to be made, packaged and delivered, as the mRNA will make more copies of itself once inside our cells. This is the next generation of mRNA vaccines after the “standard” mRNA vaccines seen so far against COVID-19.

3. Cancer vaccines

We already have vaccines that prevent infection with viruses that cause cancer. For example, hepatitis B vaccine prevents some types of liver cancer and the human papillomavirus (HPV) vaccine prevents cervical cancer.

But the flexibility of mRNA vaccines lets us think more broadly about tackling cancers not caused by viruses.

Some types of tumours have antigens or proteins not found in normal cells. If we could train our immune systems to identify these tumour-associated antigens then our immune cells could kill the cancer.

Cancer vaccines can be targeted to specific combinations of these antigens. BioNTech is developing one such mRNA vaccine that shows promise for people with advanced melanoma. CureVac has developed one for a specific type of lung cancer, with results from early clinical trials.

Then there’s the promise of personalised anti-cancer mRNA vaccines. If we could design an individualised vaccine specific to each patient’s tumour then we could train their immune system to fight their own individual cancer. Several research groups and companies are working on this.

Yes, there are challenges ahead

However, there are several hurdles to overcome before mRNA vaccines against other medical conditions are used more widely.

Current mRNA vaccines need to be kept frozen, limiting their use in developing countries or in remote areas. But Moderna is working on developing an mRNA vaccine that can be kept in a fridge.

Researchers also need to look at how these vaccines are delivered into the body. While injecting into the muscle works for mRNA COVID-19 vaccines, delivery into a vein may be better for cancer vaccines.

The vaccines need to be shown to be safe and effective in large-scale human clinical trials, ahead of regulatory approval. However, as regulatory bodies around the world have already approved mRNA COVID-19 vaccines, there are far fewer regulatory hurdles than a year ago.

The high cost of personalised mRNA cancer vaccines may also be an issue.

Finally, not all countries have the facilities to make mRNA vaccines on a large scale, including Australia.

Regardless of these hurdles, mRNA vaccine technology has been described as disruptive and revolutionary. If we can overcome these challenges, we can potentially change how we make vaccines now and into the future.

Archa Fox, Associate Professor and ARC Future Fellow, The University of Western Australia and Damian Purcell, Professor of virology and theme leader for viral infectious diseases, The Peter Doherty Institute for Infection and Immunity

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Tag Archives: mRNA

Why can’t Australia make mRNA vaccines? Because we don’t make enough ‘deep technology’ companies

What is deep technology

Australia’s problem with deep tech

The ‘valley of death’

What can we do about it?

What’s Australia’s first local Pfizer-style COVID vaccine? And when might it be in our arms? An mRNA expert explains

It’s based on existing technology

How do mRNA vaccines work again?

What are the next steps?

Why we need Australian-made vaccines

Research now backs routinely offering pregnant women the mRNA COVID-19 vaccine

Prioritising pregnant women

Changing advice to pregnant women

Can the Pfizer or Moderna mRNA vaccines affect my genetic code?

Remind me, how do mRNA vaccines work?

Here’s why the mRNA can’t insert into your genetic code

But aren’t there some exceptions?

How do we actually know this?

So how did this myth come about?

The world is hungry for mRNA COVID vaccines like Pfizer’s. But we’re short of vital components

The shortages slowing mRNA vaccine production

Why do we have these shortages?

How could these shortages impact future mRNA manufacturing in Australia?

How mRNA Vaccines Work

3 mRNA vaccines researchers are working on (that aren’t COVID)

Remind me again, what’s mRNA?

1. Flu vaccine

2. Malaria vaccine

3. Cancer vaccines

Yes, there are challenges ahead

Sharing my thoughts with the world from a Particular Baptist perspective

What is deep technology

Australia’s problem with deep tech

The ‘valley of death’

What can we do about it?

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It’s based on existing technology

How do mRNA vaccines work again?

What are the next steps?

Why we need Australian-made vaccines

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Prioritising pregnant women

Changing advice to pregnant women

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Remind me, how do mRNA vaccines work?

Here’s why the mRNA can’t insert into your genetic code

But aren’t there some exceptions?

How do we actually know this?

So how did this myth come about?

Share this:

Like this:

The shortages slowing mRNA vaccine production

Why do we have these shortages?

How could these shortages impact future mRNA manufacturing in Australia?

Share this:

Like this:

Share this:

Like this:

Remind me again, what’s mRNA?

1. Flu vaccine

2. Malaria vaccine

3. Cancer vaccines

Yes, there are challenges ahead

Share this:

Like this: