Coronavirus Update: Australia

What do I need to know about the Moderna vaccine? And how does it compare with Pfizer?

Archa Fox, The University of Western Australia and Thomas Preiss, Australian National UniversityAustralia’s medical regulator has provisionally approved another COVID-19 vaccine, Moderna, for use in Australia.

One million doses of Moderna are due in the second half of September and three million doses a month will begin to arrive from October.

Read more:
Australia’s vaccines boosted with provisional approval for Moderna

Like Pfizer, Moderna is an mRNA vaccine. So how does it work, and what are the similarities and differences with Pfizer?

Remind me, how do mRNA vaccines work?

mRNA is a temporary genetic instruction that tells our cells to make a particular protein. It consists of a central portion with the genetic code for the protein and shorter portions either side that are important for the “readability” of the code.

The mRNA is wrapped in an oily coat that helps it enter our cells. The mRNA gets broken down quite quickly after it is delivered and used.

The Pfizer and Moderna vaccines were designed with the same goals and principles: to make an mRNA (genetic instruction) for the spike protein found on the surface of the SARS-CoV-2 virus (which causes COVID-19).

A SARS-CoV-2 virus with red spike proteins.
The SARS-CoV-2 virus is covered in spike proteins, shown here in red.

Body cells near the vaccine injection site will make the spike protein, display it on their surface and trigger the immune system to learn how to fight the actual virus if it encounters it.

Do Pfizer and Moderna work any differently?

The vaccines are remarkably similar overall, with just a few technical differences. The two mRNAs are based on the same chemistry and produce the same spike protein variant.

But the mRNA sequences differ in two ways: the exact “wording” of the genetic code for the spike protein; and the shorter portions outside the actual genetic code that determine its “readability”.

The two companies also use different oily coatings in their formulations.

How many doses for Moderna? And how far apart?

Despite their similarities, the Moderna doses have more than three times the amount of mRNA material (100 micrograms), compared to Pfizer (30 micrograms).

The dose spacing is also different: three weeks apart for Pfizer and four weeks for Moderna.

These differences may be due to those small technical differences highlighted above.

Alternatively, given the great urgency of developing and trialling the vaccines, it’s also plausible both manufacturers ran out of time to fully test different formulations and timelines, and simply went with the amounts and spacing that produced the desired results.

How effective is Moderna at preventing COVID-19?

Large phase 3 clinical trials showed the Moderna vaccine was 94% effective at preventing severe disease, and Pfizer was 95% effective.

Read more:
What is the Moderna COVID vaccine? Does it work, and is it safe?

Newer studies based on real-world data of millions of vaccinated people in many countries have shown Moderna and Pfizer vaccines are:

  • 80-90% effective at preventing asymptomatic infection
  • 90% effective at preventing symptomatic infection
  • 95% effective at preventing hospitalisation.

The Moderna vaccine has been approved for emergency use in many countries including the United States, many European Union countries, Canada, the United Kingdom, Israel and India, among others.

Several studies, only some of which have been peer-reviewed, indicate both Pfizer and Moderna vaccines are highly effective against the Delta variant, although there is a slight reduction compared to the original viral strain.

Are there any side effects?

Both vaccines have some side effects common to most vaccines, including some soreness at the injection site, fatigue and headaches.

There is an association, but not a causal link between a slight increase in incidence of myocarditis (inflammation of heart muscle) and pericarditis (inflammation of the lining of the heart) with both Pfizer and Moderna vaccines.

These conditions are more common in young men and are generally treatable and not fatal; most patients make a swift recovery.

Read more:
The benefits of a COVID vaccine far outweigh the small risk of treatable heart inflammation

For both Moderna and Pfizer vaccines the rates of anaphylaxis (extreme allergic reaction) are similar, and extremely low (two to four cases per million).

How long does the immunity last?

Moderna recently announced no change in efficacy six months after participants received their COVID-19 vaccines, with a 93% protection against severe disease after six months, compared to 94% reported in the clinical trial.

Pfizer has reported similar data, with protection sitting at 84% after six months.

No longer term effectiveness studies have been possible, as the wide-scale vaccine rollout only commenced at the end of 2020.

What about storage and transport?

Moderna requires a -50°C to -15°C range during transport and long-term storage (until the expiration date is reached) and this can be achieved with standard freezers.

In contrast, the Pfizer vaccine needs to be transported and stored at temperatures below -60°C, needing dry ice and ultra-cold freezers. Then, undiluted Pfizer vaccine can be stored in a regular freezer (between -25°C and -15°C) for up to two weeks, or in a fridge (between 2°C and 8°C) for up to four weeks.

How much Moderna is coming to Australia?

Moderna is approved for use in adults aged 18 and over. Australia’s medicines regulator, the Therapeutic Goods Administration (TGA) is currently reviewing an application from Moderna to approve the vaccine’s use in children aged 12 and over.

Prime Minister Scott Morrison says planning is underway for Moderna vaccines to be rolled out through approved pharmacies and other providers from September, after the government receives advice from its immunisation advisory group ATAGI.

Ten million Moderna doses will arrive during 2021: one million in the second half of September and nine million doses due by December.

That compares with plans to roll out four million Pfizer doses in September, ten million in November and six million in December.

Next year, 15 million Moderna doses are due to arrive; these will be reserved as booster shots. A further 60 million Pfizer doses will also be available in 2022.

It’s likely Australians in eligible groups will be offered either Moderna or Pfizer and given their similarities, it really doesn’t matter which one you have – they’re both very effective.

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

The Conversation

Archa Fox, Associate Professor and ARC Future Fellow, The University of Western Australia and Thomas Preiss, Molecular biologist, Australian National University

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

Australia’s vaccines boosted with provisional approval for Moderna

Michelle Grattan, University of CanberraThe Moderna vaccine has been provisionally approved by the Therapeutic Goods Administration for use in Australia, with one million doses due in the second half of September, which will go to pharmacies.

Three million doses are then scheduled to arrive in each of October, November, and December, with 15 million booster doses in the first half of next year.

Health Minister Greg Hunt said Moderna, an mRNA vaccine, was expected to be available for eligible people from next month, after final advice from the Australian Technical Advisory Group on Immunisation (ATAGI). Moderna has been approved for people 18 and over.

The TGA is also considering Moderna for children, with the head of the TGA Dr John Skerritt saying a decision on its suitability for those 12 and over is expected within the next three to four weeks.

Skerritt said very recently Europe had recommended Moderna’s use for children over 12.

“We made the decision in conjunction with the company to do the adults first because that enabled us to reach a decision earlier, which can then start the whole process of access to the vaccine in Australia earlier. The data on the teenagers does look good,” he said.

Skerritt said even after six months, Moderna was 93% effective against infection, 98% against severe disease and 100% against death. Two doses are required, 28 days apart.

The Moderna announcement came as NSW recorded 283 new locally acquired cases.

Skerritt also said the TGA was working with industry on the wider availability of rapid antigen tests.

“These tests are not the gold standard PCR tests,” he said, but they were a useful adjunct. “Clearly there are a range of things that have to be resolved, such as collection and recording of data.”

The Australian Industry Group’s CEO, Innes Willox, said it was urgent that rapid testing be fully approved as soon as possible.

“Results are very close to lab based tests, almost instantaneous and from the employer’s perspective that means they can be used in some high risk operations at the beginning of a shift or in operations every week or so,” Willox said.

Willox also called on the government “to extend the same indemnity to employers who vaccinate their willing workers at the workplace as is enjoyed by doctors, pharmacists and pharmaceutical companies.

“A medical practitioner who comes to a workplace to give the vaccine would have an indemnity. The employer does not have that same indemnity but should be given it to cover any unexpected circumstances.”

He stressed indemnity had nothing to do with mandating vaccinations.

Morrison, who took another knock in the latest Newspoll in his personal ratings and for his handling of COVID, said the Delta variant has changed everything. “It’s changed all of the rules and it means we’ve had to change with it to keep Australians safe. And, that means, right now, we are going through one of the toughest parts of this COVID pandemic,” he said.

“I know Australians are frustrated. I know they’re sick of it. I know they’re angry. And I know they want it to stop and for life to get back to where they knew it. But, what we have to do now is recognise the reality of the challenge we have in front of us. None of us likes it.”The Conversation

Michelle Grattan, Professorial Fellow, University of Canberra

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

Coronavirus Update: Australia

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


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.

Read more:
What is mRNA? The messenger molecule that’s been in every living cell for billions of years is the key ingredient in some COVID-19 vaccines

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.

Read more:
Not sure about the Pfizer vaccine, now it’s been approved in Australia? You can scratch these 4 concerns straight off your list

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.

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.

Read more:
4 things about mRNA COVID vaccines researchers still want to find out

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.

Read more:
Will the COVID vaccine make me test positive for the coronavirus? 5 questions about vaccines and COVID testing answered

The Conversation

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.

What is the Moderna COVID vaccine? Does it work, and is it safe?

Adam Taylor, Griffith UniversityOvernight, Boston-based pharmaceutical company Moderna announced a new supply agreement with Australia for 25 million doses of its COVID-19 vaccine.

The deal includes ten million doses against the original strain of the coronavirus to be delivered this year.

This vaccine has been widely used in countries such as Canada, United States and the United Kingdom under emergency use authorisations granted by these countries and the World Health Organization.

Moderna’s deal with Australia also includes 15 million doses of its updated variant booster vaccine candidate, estimated to be delivered in 2022.

The agreement is subject to approval by Australia’s drug regulator, the Therapeutic Goods Administration (TGA), for both the original vaccine and the booster. Moderna expects to submit an application to the TGA “shortly”.

How does Moderna’s vaccine work?

Moderna’s vaccine against the original strain is given as two doses.

Both this vaccine, and the updated booster, are mRNA vaccines (like the Pfizer vaccine). The vaccine contains genetic instructions for our cells to make the coronavirus’ “spike protein”. The mRNA is wrapped in an oily shell that protects it from being immediately degraded by the body, and ensures it’s delivered into cells after injection.

Once in the cell, the mRNA is converted into spike protein that can be recognised by the immune system. Our immune system then builds an immune response against the spike protein, and learns how to fight off the coronavirus if we encounter it in future.

Moderna’s vaccine remains stable at -20°C, the temperature of a household freezer, for up to six months. It can remain refrigerated at 4°C for up to 30 days.

As most pharmaceutical logistic companies are capable of storing and transporting products at -20°C, it’s relatively easy to store and distribute this vaccine. By contrast, Pfizer’s mRNA COVID-19 vaccine needs to be stored long-term below -60°C, though unopened vials can be stored at freezer temperatures for up to two weeks.

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

Is it safe and effective?

Phase 3 clinical trials of the vaccine, with over 30,000 participants, showed 94.1% efficacy at preventing COVID-19 as well as complete protection against severe forms of the disease.

Researchers did not identify safety concerns, with the most common side effects being transient pain at the injection site, and headache or tiredness that typically lasted for up to three days.

These clinical trials, however, largely occurred prior to the emergence of SARS-CoV-2 variants of concern. These include B.1.1.7, which emerged from the United Kingdom, and B.1.351, first detected in South Africa.

Read more:
UK, South African, Brazilian: a virologist explains each COVID variant and what they mean for the pandemic

Can it protect against variants?

Subsequent studies have investigated the potential for these variants to escape the protection offered by Moderna’s vaccine. Preliminary studies have identified slight, although not significant, reductions in the protection it offers against the B.1.351 variant, originating in South Africa.

In response to this data, Moderna updated its mRNA vaccine formulation to account for the changes in the spike protein present in the B.1.351 variant. In March this year, it started phase 1 and 2 clinical trials to investigate the safety and ability of its variant vaccine to provoke an immune response.

Preliminary, preclinical studies suggest vaccination with the variant vaccine was effective at increasing neutralising antibodies against the B.1.351 variant.

Preclinical studies also suggest a vaccine containing an equal mix of its original vaccine, and the B.1.351 vaccine, was most effective at providing broad cross-variant protection, including against the P.1 variant that originated in Brazil.

In people already fully vaccinated against the original strain, clinical studies demonstrated a booster dose of Moderna’s variant vaccine achieved a higher number of neutralising antibodies against the B.1.351 variant, than simply giving a booster dose of Moderna’s original strain vaccine.

Moderna’s vaccines can be rapidly reformulated to target emerging variants. This is largely thanks to the splendour of the mRNA technology, simply requiring the genetic sequence of the virus.

It’s possible Moderna will be able to update its vaccine to cover future variants of the coronavirus so we can quickly provide people with protection to emerging strains.

Read more:
3 doses, then 1 each year: why Pfizer, not AstraZeneca, is the best bet for the long haul

Moderna revealed it’s in discussions with the federal government about manufacturing its vaccines onshore in Australia. This follows news that both Victoria and New South Wales have committed money towards developing mRNA vaccine manufacturing capability.

This is a move that would not only further secure Australia’s supply of COVID-19 vaccines, but kick start the development of an industry within Australia that has the potential to impact multiple diseases.The Conversation

Adam Taylor, Early Career Research Leader, Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University

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

Moderna’s COVID vaccine reports 95% efficacy. It means we might have multiple successful vaccines

Magdalena Plebanski, RMIT University and Vasso Apostolopoulos, Victoria University

American biotech firm Moderna has released early results from its phase 3 clinical trials, announcing in a press release on Monday (US time) that its COVID vaccine has an efficacy of 94.5%, according to an “interim analysis” by an independent data and safety monitoring board.

Here’s how the percentage was calculated. First, there are two groups in the study: the vaccinated group, who received the candidate vaccine, and the placebo group, who received a shot of salt water.

Among 30,000 trial participants, 95 people developed COVID just in the one week after the final vaccination. But encouragingly, 90 of those positive cases occurred in the placebo group, and only five were in the vaccinated group.

While this is good news, many questions remain. We don’t yet know how long protection against the virus will last with this vaccine. We also don’t know for sure whether this vaccine is safe and effective in different types of people, such as pregnant women, the elderly, or those with a chronic illness.

Once a vaccine is deployed “in the real world”, we’ll start to understand its true effectiveness. In practice, this is likely to be different to its efficacy in highly controlled clinical trials.

Thus far, we can only say the Moderna vaccine prevents COVID symptoms, as only volunteers who developed symptoms in this trial were analysed. We don’t know for sure if it can prevent infection altogether.

Vaccines that control disease symptoms, rather than stopping infectious viruses from being transmitted from person to person, are valuable. But it is “transmission-blocking” vaccines that are most effective at rapidly reducing viral spread and have the highest chance of eliminating a pathogen from a population.

Moderna’s is easier to distribute

Like Pfizer’s vaccine, Moderna’s is an mRNA vaccine.

The company is co-developing it with the National Institute of Allergy and Infectious Diseases, part of the US federal health department.

The practical advantage Moderna appears to have over Pfizer is that its temperature requirements for distribution are simpler: 4℃ rather than -70℃. Storing and transporting a vaccine at 4℃ initially — the temperature of a household fridge — is much easier. By contrast, -70℃ freezers may only be found at major hospitals. For storage beyond 30 days the Moderna vaccine needs to be kept at -20℃, but even -20℃ freezers can be secured more easily.

However, while both vaccines seem to induce neutralising antibodies against the SARS-CoV-2 “spike protein”, both report relatively poor induction of the other arm of the immune response: T cells that can target the virus, particularly those that can do it after the virus has hidden inside cells.

What’s more, neither vaccine has been shown to perform as well in older people compared to young adults. As a matter of fact, early phase 1 and 2 trials of the Pfizer vaccine saw the vaccine perform half as well in older individuals for antibody production.

Moderna’s latest human trial assessing safety and the vaccine’s ability to induce immune responses, which published final results in September after peer review, showed its vaccine induced the production of a similar amount of antibodies in adults under 70 years old, compared with those over 70. This is great news.

However, the shot induced significantly fewer T cells in adults over 71, particularly the type of T cells expected to be able to kill virus infected cells. Thus far, it’s not known whether this will result in less protection or less sustained immunity, but it is concerning this vaccine could be potentially less effective in older people.

Read more:
Australia may miss out on several COVID vaccines if it can’t make mRNA ones locally

We might end up with multiple successful vaccines

We now have two mRNA COVID vaccines with greater than 90% reported efficacy, according to early phase 3 trial results.

It’s great news that multiple vaccines in the pipeline are showing good results. It opens the door to the possibility we might have many successful vaccines, and be able to tailor different vaccines to people with different needs.

Read more:
90% efficacy for Pfizer’s COVID-19 mRNA vaccine is striking. But we need to wait for the full data

There are still more than 200 COVID vaccine candidates, many of which use different processes and types of technology. Some of these will work better for different people, for example older people, pregnant women or people with chronic diseases.

For example, the “adenovirus” vaccines, of which the Oxford University vaccine is one, seems to be good at inducing T cells.

And the University of Queensland’s vaccine looks well placed to induce immune responses specifically in older people.

Tailoring different vaccines to different people will help us increase coverage and hopefully increases the likelihood we can eliminate this virus safely.

The Australian federal government has formed a key group, the Australian Technical Advisory Group on Immunisation for COVID, which will be able to advise on which vaccines might be best for which people.The Conversation

Magdalena Plebanski, Professor of Immunology, RMIT University and Vasso Apostolopoulos, Professor of Immunology and Pro Vice-Chancellor, Research Partnerships, Victoria University

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