COVID vaccines have been developed in record time. But how will we know they’re safe?



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Nicholas Wood, University of Sydney and Kristine Macartney, University of Sydney

With the rollout of COVID-19 vaccines about to begin in Australia, people may be wondering if they’re safe (and effective) in the long term. What might be the health consequences a year after vaccination, or further into the future?

While it’s true COVID-19 vaccines have been developed in record time, the importance of tracking vaccine safety is not new. We routinely monitor the safety of all vaccinations, years after they’ve been used in millions of people.

And in guidance from the Therapeutic Goods Administration (TGA) this week, we have a clearer picture of how we’ll know about any unexpected, rare or long-term side-effects of the COVID-19 vaccines. In fact, we’ll use and build on many existing systems to look out for these.




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Vaccine trials only tell us so much

Late-stage vaccine trials in tens of thousands of people only last for a defined period of time, typically 12 months. Vaccine manufacturers present data on vaccine safety (and efficacy) for that time-frame to regulatory bodies. Safety data is rigorously assessed before a vaccine is approved for use.

But when approved vaccines are then given to the general public, we can monitor for any new events that may occur unexpectedly in both the short and longer term. Tracking potential side-effects in the real world in all people who have a vaccine, and outside the tightly controlled conditions of a trial, means we can ensure the vaccine is safe when given to millions — or billions — of people.




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So how might this work for COVID-19 vaccines? The Pfizer/BioNTech vaccine phase 3 trial reported safety data until about 14 weeks after the second dose. The Oxford/AstraZeneca trial reported safety data after about three months after the first dose, and two months after the second dose.

However, participants in both these large trials will continue to be followed up for both efficacy and safety until the end of the study from around 12 months after the first dose of vaccine.

COVID vaccine safety is also being monitored in several other ways, by individual countries, including Australia. Countries also share their vaccine safety monitoring data via a global database.




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Here’s how we’ll monitor COVID vaccine safety in Australia

The TGA has overall responsibility for monitoring the safety of medicines and vaccines in Australia. Just this week, the TGA released its plans for monitoring the safety of COVID-19 vaccines.

This includes the timely collection and management of reports of COVID-19 vaccine adverse events, an ability to urgently detect any safety concerns and to communicate safety issues to the public.

‘Passive’ surveillance

A cornerstone of the system Australia has had in place for decades to capture any possible vaccine reactions is “passive” surveillance. In practice, this means anyone can report a reaction to the TGA, the public included.

If your GP or nurse thinks you may have had a reaction they should report this to their state or territory health department, which then informs the TGA. This is mandatory in some jurisdictions but not in others.

Woman holding smartphone about to make a call
Consumers are being encouraged to report any suspected side-effects after their COVID vaccine.
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The TGA is encouraging health professionals and consumers to report suspected side-effects to COVID-19 vaccines and there is a guide on its website on how to do this.

The TGA has a database that records any reported possible reactions. If there are any suspected safety issues, these are immediately investigated and necessary action is taken. For example, if necessary an immunisation program can be stopped or special precautions implemented. TGA can also issue safety alerts.

‘Active’ surveillance

Since 2014, Australia has also been actively looking for any safety concerns via the AusVaxSafety surveillance system, led by the National Centre for Immunisation Research and Surveillance, which we are affiliated with.

We send texts or emails to people asking them to fill out a survey on their health after being vaccinated. This system enables us to detect any suspected safety issues in near real time. Last year, AusVaxSafety surveyed nearly 290,000 people after they had the 2020 influenza vaccine and found more than 94% felt completely well. Others had mild and expected short-term side effects.

This system will be used to pick up any safety concerns when the COVID-19 vaccines roll out in the next few weeks. If you are vaccinated at selected sites, including GP practices and COVID-19 vaccine hubs, you will be told about this automated system. You don’t have to register or enrol but will be sent an SMS on day 3 and day 8 after each vaccine dose (you can decide whether to fill out the survey). Your anonymised results will be reported to your state or territory health department and the TGA.

This system will probably be in place to monitor safety of the COVID-19 vaccines for a few years. And as new vaccine brands come on board, we will continue to monitor those too.




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We can also learn from other countries

The United States has recently developed an equivalent system, V-safe. Safety data from this system from about two million people who have had a COVID-19 vaccine indicates the vaccines are safe. The short-term side-effects are very similar to those reported in the vaccine trials. The most common reactions include injection site pain, headache, tiredness and muscle aches, usually in the first two days and then resolving within a week after vaccination.

And worldwide, more than 150 million COVID-19 vaccine doses have already been given, with no unexpected safety concerns.




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In a nutshell

The potential benefits to us all from a mass vaccination program against COVID-19 far outweigh the potential side-effects, based on data from millions of people who have already been vaccinated around the world. Yet, we know all medicines, vaccines included, have the potential for side-effects.

However, by using, and building on, our already established safety surveillance system, we will be “on top” of rapidly identifying any possible safety concerns. That’s immediately after vaccination and into the longer term.The Conversation

Nicholas Wood, Associate Professor, Discipline of Childhood and Adolescent Health, University of Sydney and Kristine Macartney, Professor, Discipline of Paediatrics and Child Health, University of Sydney

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

Are vaccines already helping contain COVID? Early signs say yes, but mutations will be challenging


Maximilian de Courten, Victoria University; Maja Husaric, Victoria University, and Vasso Apostolopoulos, Victoria University

More than 130 million COVID vaccine doses have been administered worldwide already, according to the University of Oxford’s “Our World in Data” vaccination tracker.

Israel, the United Kingdom, the United States, the United Arab Emirates and China are leading this huge global effort.

COVID vaccines were initially tested and approved on their ability to reduce the severity of the disease.

However, the long-term goal of vaccination is to decrease infection rates and eliminate the virus.

Excitingly, early signs suggest vaccines are already helping drive down infection rates in some countries, including Israel and the UK.

In saying that, it’s early days, and some preliminary data suggest countries might have to update their vaccine strategies to deal with emerging variants of the virus.

Israel is leading the way

The US (43 million doses), China (40 million) and the UK (13 million) have administered the most doses in total.

However, these numbers don’t take into account population size, so looking at the number of doses injected per 100 people is more meaningful.

Here, the league table is currently topped by Israel, with around 67 vaccination doses administered per 100 people.

Almost 25% of the population are fully vaccinated with both doses. And all this in just five weeks.

Israel aims to vaccinate everyone over the age of 16 and reach at least 80% of its nine million people by May this year.

Reaching at least 70% of the population via vaccination (and/or natural infection) is needed for herd immunity for COVID, according to initial modelling by University of Chicago researchers in May last year.

However, given more infectious variants of the virus have emerged, we may need to vaccinate an even higher proportion of the population to reach herd immunity.

Infection rates are falling

So far, Israel is solely using the Pfizer/BioNTech vaccine. Interim reports from the country suggest the vaccine rollout is linked to a fall in infections in people over 60 years old.

It can be tricky to separate the effects of public health measures such as lockdowns versus the effects of vaccination.

But because the fall is most pronounced in older people who were first in line to receive the vaccine, data suggest this is also partly due to the vaccine, and not just the country’s current restrictions. A team of Israeli researchers found larger falls in infections and hospitalisations after the vaccinations than occurred during previous lockdowns.

Only 0.07% of the 750,000 over-60s vaccinated tested positive for COVID, according to Israeli Ministry of Health data released last week. And only 38 people, or 0.005%, fell ill and required hospitalisation. The chance of testing positive for COVID two weeks after receiving the first dose was 33% lower than in those not vaccinated.

The UK is also showing positive signs

The UK has administered 19.4 doses per 100 people. Around 13.2 million people (or one in five adults) have received the first dose, and 0.5 million have received the second dose.

It’s currently using both the Pfizer/BioNTech and Oxford University/AstraZeneca vaccines in its rollout.

The infection rate appears to be decreasing substantially. The current daily infection growth rate is falling by between 2-5%, and the R number is estimated to be between 0.7 and 1 (an R number of less than 1 means daily new cases will decrease over time).

However, it’s difficult to determine whether these numbers are due to the lockdown or vaccinations. It’s too early to tell whether vaccines are slowing transmission, but the signs are encouraging.

According to data from the Oxford/AstraZeneca vaccine group, released as a preprint with The Lancet last week and yet to be peer reviewed, its vaccine is showing signs of reducing transmission. The shot was associated with a 67% reduction in transmission among vaccinated volunteers in clinical trials in the UK.

It’s early days, but authors of the study suggest the vaccine may have a “substantial” effect on reducing rates of transmission in the future.

In saying that, preliminary data suggest it offers minimal protection against mild or moderate illness caused by the South African variant.




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What threatens the successful rollout of vaccines?

There are three main problems that might hinder the success of this global vaccination drive.

1. Vaccine development, manufacturing, distribution and delivery

The world’s population over the age of five is currently estimated at seven billion people. If we need to vaccinate at least 70% of them to achieve herd immunity, we need to reach around five billion people.

This is an enormous undertaking, so vaccine production and availability are crucial. Many countries face the massive challenge of producing or securing enough vaccines to immunise all their citizens.

Generally, wealthier countries that could afford to make advanced purchase agreements with vaccine producers — or who could manufacture a vaccine domestically — have been the first to start COVID vaccinations.

Unfortunately, partial vaccination of the world’s population won’t achieve herd immunity. One modelling study suggests if high-income countries exclusively acquire the first two billion doses without regard for vaccine equity, the number of COVID deaths could double worldwide.

2. Administering, monitoring, and reporting adverse effects

Vaccinating a large number of citizens quickly can’t be done with existing health institutions alone.

It’s urgent we enable alternative sites such as halls and sporting venues to be used as mass vaccination sites. We also need to allow a range of health professions such as medical students, public health officials and pharmacists to administer doses to help speed up the process.

And once vaccines have been administered, it’s crucial we monitor efficacy and report on any adverse effects, which will require additional resources.




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3. Vaccine effectiveness and virus mutation

The effectiveness of vaccines can be hindered by mutations of the virus. COVID variants originating in Brazil, South Africa, and the UK have triggered huge concern worldwide.

There’s early evidence some of our current crop of COVID vaccines respond less effectively to certain variants, though most of these data are preliminary and are still emerging.




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If vaccines become less effective, new vaccines will need to be developed either including a booster dose incorporating the region of the mutated virus, or reformulating existing vaccines to include the mutated strains.

This, however, isn’t uncommon — flu vaccines are required to be updated regularly in order to increase protective capacity against new mutated strains.The Conversation

Maximilian de Courten, Professor in Global Public Health and Director of the Mitchell Institute, Victoria University; Maja Husaric, Senior Lecturer; MD, Victoria 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.

The Oxford vaccine has unique advantages, as does Pfizer’s. Using both is Australia’s best strategy


Kylie Quinn, RMIT University; Holly Seale, UNSW, and Margie Danchin, Murdoch Children’s Research Institute

On Sunday, federal Chief Medical Officer Professor Paul Kelly said most Australians will be offered a vaccine from Oxford-AstraZeneca.

Australia currently has agreements in place to receive 53.8 million doses of the AstraZeneca shot, and 10 million doses from Pfizer-BioNTech.

So how do these two vaccines compare, how will they be used in Australia, and what can we learn from other vaccines?




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Comparing the two

Both the Pfizer and AstraZeneca vaccines induce immunity but in different ways. They both deliver the instructions for how to make a target on the virus for our immune system to recognise the spike protein.

The Pfizer vaccine packages the instructions up in a droplet of fat, while the AstraZeneca vaccine packages the instructions up in the shell of a virus, the adenovirus.

Clinical trials for both vaccines have shown they’re broadly safe.

In terms of efficacy, the Pfizer vaccine protects 94.5% of people from developing COVID.

The AstraZeneca shot protects 70% of people on average — still pretty good and on par with the protection given by a flu vaccine in a good year.

However, the optimal dose and timing of AstraZeneca’s shots is still unclear. One trial reported 62% efficacy, and another 90%, with a low dose for the first shot and/or longer break between doses possibly improving protection. More studies are underway to define this and the Therapeutic Goods Administration, Australia’s regulatory body, will evaluate new data as it comes through.

In any scenario, the AstraZeneca vaccine will still protect the majority of people that receive the vaccine from disease.




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While the Pfizer vaccine was more protective in clinical trials, the AstraZeneca vaccine has other advantages that could make it more appropriate for use outside of clinical trials:

From a logistical perspective, the AstraZeneca vaccine has a major advantage. The ability to distribute vaccines can be almost as important as the vaccine’s effectiveness.

The effect of these advantages on the impact of this vaccine shouldn’t be underestimated. We have lots of people to vaccinate, a low disease burden currently, are far away from the rest of the world in terms of shipping, and Australia is a pretty big country, so distribution to rural and remote communities is a massive hurdle.

Efficacy isn’t the only thing we should consider

It can be helpful to look at the flu vaccine as a contrast. The flu vaccine is far from perfect — it provides moderate protection, with effectiveness varying between different groups of people and from season to season. For example, in the 2015/16 season in the United States, the quadrivalent influenza vaccine (which covers four strains) was about 54% effective against laboratory-confirmed influenza.

People know it’s not perfect, but people don’t generally judge whether they’ll receive a vaccine based on its effectiveness alone. We know from talking to the community that many factors influence motivation, especially perceived risk and severity of infection, and confidence in the safety of the vaccine.

Every year, access to flu vaccines is prioritised to those at most risk, such as people with medical conditions, Aboriginal and Torres Strait Islanders and those aged 65 years and older. The public has confidence in this approach. We need to protect those most at-risk first, and we don’t have an issue doing this day-to-day. We now have a similar challenge with the new COVID vaccines.

The best approach for protecting everyone’s health amid the pandemic is to provide different vaccines to different people according to need and availability, at least in the short term. The best vaccine is always the one you can get to the communities that need it before they urgently need it.

Australia’s combination strategy

Because Australia is essentially COVID-free at present, it means we’re in a unique situation that permits a “combination” vaccine strategy.

The Pfizer vaccine is perfect for preventing the most extreme outcomes for people at very high risk of infection or disease: people on the frontlines of the fight against COVID and older people or people with high-risk health conditions.

The AstraZeneca vaccine has the ability to protect a large number of people against disease quickly, because we can make it easily and distribute it quickly.

As a result, Pfizer is likely to be prioritised for people with higher risk and AstraZeneca is likely to be prioritised for everyone else.

We won’t all be able to get the Pfizer vaccine straight away, so for many of us the choice in the short term will be between a 70% efficacious vaccine or no vaccine.

We all stand to benefit from a strategy that protects extremely vulnerable groups from severe disease and aims to rapidly generate immunity in the rest of our community.

There may also be other vaccines that become available. Australia is part of COVAX which can distribute a variety of vaccines, and it also has an agreement for a vaccine made by Novavax, pending the outcome of phase 3 clinical trials. There could be other vaccines that emerge or other agreements developed, and Australia’s strategy will no doubt respond to that.




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Nevertheless, both the Pfizer and AstraZeneca vaccines are essential tools in our public health toolkit, with vital roles to play in protecting the entire Australian population. We’ll also need to continue to use other public health tools like testing and contact tracing.

Factoring in effectiveness, availability and distribution challenges, a strategy that uses a combination of the two vaccines for Australia is the best of both worlds.


Shane Huntington co-authored this article. He is Deputy Director, Strategy and Partnerships, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne.The Conversation

Kylie Quinn, Vice-Chancellor’s Research Fellow, School of Health and Biomedical Sciences, RMIT University; Holly Seale, Associate professor, UNSW, and Margie Danchin, Associate Professor, University of Melbourne, Murdoch Children’s Research Institute

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

The top scientific breakthrough for 2020 was understanding SARS-CoV-2 and how it causes COVID-19 – and then developing multiple vaccines



The number one scientific breakthrough for 2020: multiple vaccines to prevent COVID-19.
Philippe Raimbault/Photodisc via Getty Images

David Pride, University of California San Diego

SARS-CoV-2, the virus that causes the respiratory illness COVID-19, has killed approximately 2.2% of those worldwide who are known to have contracted it. But the situation could be a lot worse without modern medicine and science.

The last such global scourge was the influenza pandemic of 1918, which is estimated to have killed 50 million people at a time when there was no internet or easy access to long-distance telephones to disseminate information. Science was limited, which made it difficult to identify the cause and initiate vaccine development. The world is 100% more prepared for the current pandemic than it was 100 years ago. However, it has still affected our lives profoundly.

I am a physician scientist who specializes in the study of viruses and runs a microbiology laboratory that tests for SARS-CoV-2 infections. I’ve seen firsthand patients with severe COVID-19 illness and have dedicated myself to developing diagnostics for this disease. It’s a remarkable testament to science that a novel disease-causing virus has been discovered, the genetic material completely decoded, new therapies created to fight it and multiple safe and effective vaccines developed all within the span of a year – an accomplishment that the journal Science has pegged the breakthrough of 2020.

Most vaccines take 10-15 years to develop. Until now the fastest vaccine developed was against the mumps virus, which took four years. Now, in the midst of the SARS-CoV-2 pandemic, one vaccine is already authorized for use in the U.S., with a second close behind. Other vaccines have already been rolled out in countries across the globe.

Science fast-tracked

This pandemic put science front and center. One of the most significant scientific advances in the past 15 years has been the ability to read the genetic instructions – or genome – that encode viruses. The process of sequencing the genome of a virus is called next generation sequencing, and it has revolutionized science by allowing researchers to rapidly decode the genome of a virus or bacterium, quickly and cost-effectively. This strategy was used to determine the sequence of SARS-CoV-2 early in January 2020 before epidemiologists even recognized that it had already spread around the world. Obtaining the sequence allowed for the rapid development of diagnostics for SARS-CoV-2 and to figure out who was infected and how the virus might spread.

SARS-CoV coronavirus was responsible for an outbreak that spanned 2002-2004, but was not particularly contagious and was limited mostly to Southeast Asia.

SARS-CoV-2 has evolved two separate qualities that allow it to spread more easily. First, it has an enormous potential for triggering asymptomatic infections, in which the virus infects carriers who don’t experience symptoms and may never know they are infected and transmitting the virus to others.

Second, it can spread via aerosolized particles. Most of these viruses spread via large respiratory droplets, which are visible and fall out of the air within three to six feet. But SARS-CoV-2 can also spread through airborne transmission via much smaller particles that remain in the air for several hours.

While in 1918 people went on blind faith that masking reduced transmission, this time around, science provided us with concrete answers. There have been several studies demonstrating the efficacy of masking. These types of studies inform the public that mask-wearing, social distancing, hand-washing and limiting crowd sizes decrease circulating virus and thus reduce hospitalizations and death. While they don’t get much fanfare, these studies are among the most important discoveries in response to this pandemic.

Masks work for cutting transmission of the coronavirus.
F.J. Jimenez/Moment via Getty Images

Science aids diagnostics

Many tests for the virus are performed using PCR, which is short for polymerase chain reaction. This method uses specialized proteins and virus-matching DNA sequences called primers to create more copies of the virus. These additional copies allow PCR machines to detect the presence of the virus; doctors can then tell you if you are infected. Because of the availability of the virus’s genome sequence, any researcher can design primers that match the virus to develop a diagnostic test.

Early on, the World Health Organization developed a PCR test to detect the virus and disseminated instructions on how to use it to researchers and physicians around the globe.

This was a remarkable achievement that allowed countries across the world to rapidly develop diagnostic tests using this template. This distribution changed the course of the pandemic in many countries.

Treatments have lowered mortality rates

Treatments for infectious diseases often evolve over time. There is no vaccine yet for hepatitis C, but over recent years treatments have evolved from those that make you very ill to those that are highly efficacious with few side effects.

We are now seeing similar things in the SARS-CoV-2 pandemic, just on an accelerated timeline. With the aid of clinical studies, we now have treatments such as steroids, antiviral medications like Remdesivir and infusions of antibodies. Physicians also know how to alter a patient’s position in ways that increase the chance of survival.

COVID-19 patient Michael Wright lay in his bed in the prone position to increase oxygenation. Wright died in December.
Leila Navidi/Star Tribune via Getty Images

Vaccine development could end pandemic

This pandemic could end if the virus swept through the population killing millions but leaving the survivors with natural immunity. More likely the virus will snuff itself out when most of the population has been vaccinated with a SARS-CoV-2 vaccine. That is especially true in parts of the world where frequent testing and public health strategies are difficult to implement.

It took many years to develop an influenza vaccine, with the first available in 1942. Other successes with smallpox and polio, and more recent ones like HPV and Haemophilus influenzae Type b, have provided blueprints for vaccine development.

Governments across the world have partnered with private companies to expedite the development of SARS-CoV-2 vaccines. This has led to multiple different companies developing their own different versions of vaccines. Normally, these take years to develop; however, by leveraging recent successes and accumulated knowledge, the timeline was accelerated significantly. Normally, new vaccines go through phase 1 (safety), phase 2 (efficacy) and phase 3 (comparison) trials, but as demonstrated in the current trials, phases 2 and 3 can be combined for expediency. And large-scale manufacturing can begin when the vaccine is still in trials, potentially cutting years off the timeline.

Steroid medication dexamethasone is used to treat COVID-19.
Rafael Henrique/SOPA Images/LightRocket via Getty Images
One vial of the drug Remdesivir.
ULRICH PERREY/POOL/AFP via Getty Images

Technology is at the forefront of the development of these vaccines. Some of the coronavirus vaccines take advantage of mRNA technology, which essentially programs our cells to develop immune responses against SARS-CoV-2.

Others use viruses as delivery mechanisms for SARS-CoV-2 proteins to which your body develops an immune response. Both types have thus far been shown to be effective, but long-term safety will remain controversial when vaccines are developed on such an expedited timeline.

Lessons learned

This disease, which began in Wuhan, Hubei Province, China, and was first diagnosed in either November or December of 2019, is the perfect illustration of just how rapidly viruses spread in a connected world. We got previews of what could happen from the recent outbreaks of Ebola and Zika virus, but the spread of SARS-CoV-2 has been on a different level. It has underscored that when we receive warnings about contagious viruses, rapid and decisive action must be taken in all parts of the world to reduce its spread.

Where there is more strict compliance with public health policies, there have been profound reductions in virus transmission.

While the research that has made all this possible might fly under the radar right now, history will record this time as one of the greatest periods for scientific advancements.

[Understand new developments in science, health and technology, each week. Subscribe to The Conversation’s science newsletter.]The Conversation

David Pride, Associate Director of Microbiology, University of California San Diego

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

Yes, the coronavirus mutates. But that shouldn’t affect the current crop of vaccines



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Rebecca Rockett, University of Sydney; Alicia Arnott, University of Sydney, and Fabienne Brilot-Turville, University of Sydney

“Coronavirus” has already established itself as the scary new word of 2020. Add the word “mutant”, and you’ve got an even stronger candidate for the scary new phrase of 2021.

One fear is that critical parts of the coronavirus genome will mutate, making any vaccine obsolete before it’s widely rolled out next year.

But how much of an issue is this really? As we’ll see, SARS-CoV-2, the coronavirus that causes COVID-19, mutates, as do all viruses. But unlike other RNA viruses, it’s actually quite stable.

That’s largely good news for the first crop of vaccines that are set to be rolled out around the world in 2021.

What’s a mutation anyway?

In genetic terms, a mutation is just a scary word for a mistake. As cells make new copies of a virus, mistakes happen. These mistakes sometimes result in a stronger virus, sometimes a weaker virus.

But in most cases mutations in the coronavirus are irrelevant anomalies that cause changes to the genetic material (RNA) but not the resulting proteins that make up its composition and structure.

In fact, SARS-CoV-2 seems to have a slower rate of mutation than other RNA viruses. That’s because it belongs to a family of viruses with genetic proofreading mechanisms that can identify and remove most mistakes in its RNA when the virus replicates.

This means SARS-CoV-2 has about half the mutation rate of influenza and a quarter the mutation rate of HIV.




Read more:
Mutating coronavirus: what it means for all of us


What about mutations and spike proteins?

If there are lots of mutations in non-essential regions of a virus’ genetic material, it can likely still function. But mutations in critical regions can disable a virus, so these don’t occur very often.

This is why vaccines are typically designed against these critical regions — to safeguard against mutations that would make them ineffective.

And it’s mutations in one of these critical regions, the COVID-19 spike protein, that has gained significant attention recently.

This is the protein many COVID-19 vaccines use to generate a protective immune response. In fact, the four vaccines Australia has signed agreements for, should they pass clinical trials, all either contain the virus’ spike protein or carry the instructions your body needs to make it.

What’s all this to do with mink?

One mutation that has attracted controversy is the D614G mutation, partly because it leads to a spike protein with a slightly altered shape.

And some scientists were concerned this mutation, plus three others in the spike protein, would help the virus bypass the type of immunity generated following vaccination.

These mutations emerged when the coronavirus jumped from humans to minks and back again.

To avoid the potentially disastrous implications of this new combination of variants rapidly spreading in humans, millions of minks were culled in Denmark, Spain and the Netherlands.

However, not all scientists are convinced of the potential impact of this combination of mutations. So studies are currently under way to better understand their impact.




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Syringes at ten paces

Considering what we know about how the virus mutates and the rate of these mutations, the first generation of COVID-19 vaccines look likely to provide some protection against currently circulating SARS-CoV-2 strains.

However, researchers are monitoring the possible emergence of any new mutations in the spike protein from isolates around the world to ensure ongoing vaccine effectiveness.

We can identify any mutations using a technique called genome sequencing, which allows scientists to read the complete genetic sequence, or genome, of the virus.

Since January, scientists around the world have generated and made publicly available more than 246,000 COVID-19 genomes. Scientists can then compare these with the early COVID-19 genomes sequenced in Wuhan. These early sequences are the templates for the vaccines we are waiting impatiently for.

This surveillance will provide an early warning system for potentially critical mutations. And if researchers find mutations, they need to work out what these mutations actually do, using so-called “functional tests”.

Such tests can tell us whether a new mutation influences our immune response to the spike protein, compared to those induced by the original Wuhan strain. We can also investigate if antibodies following vaccination can continue to bind to the spike protein of emerging strains and prevent the virus from infecting human cells.

So should we be worried?

Researchers have only been able to study this coronavirus for a very short time. So only time will tell if it mutates at a frequency and at limited positions in the essential regions, as we have come to expect. That’s why surveillance is so important.

The current crop of vaccines have been developed using decades of accumulated scientific knowledge and are based on what we know about mutations in this and other coronaviruses. So we shouldn’t be too worried when we read scary headlines about a “mutant coronavirus”.

This past year has demonstrated the capacity to rapidly produce vaccines, which hopefully can be modified to reflect new mutations and merging strains should they occur.The Conversation

Rebecca Rockett, Virologist, University of Sydney; Alicia Arnott, Genomic Epidemiologist, University of Sydney, and Fabienne Brilot-Turville, Principal Research Fellow, University of Sydney

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

Vaccines against SARS-CoV-2 will have side effects – that’s a good thing



A little bit of post-injection soreness is completely normal.
Jose Luis Pelaez Inc/DigitalVision via Getty Images

Matthew Woodruff, Emory University

Takeaways

  • Temporary side effects from vaccines are a normal sign of a developing immune response.

  • Vaccines work by training your immune system to recognize and remember a pathogen in a safe way.

  • Expected side effects from a COVID-19 vaccine include redness and swelling at the injection site and stiffness and soreness in the muscle.

  • A potent vaccine may even cause fever. It does not mean that the vaccine gave you COVID-19.


In 2021 hundreds of millions of people will be vaccinated against SARS-CoV-2. The success of that COVID-19 vaccination campaign will heavily depend on public trust that the vaccines are not only effective, but also safe. To build that trust, the medical and scientific communities have a responsibility to engage in difficult discussions with the public about the significant fraction of people who will experience temporary side effects from these vaccines.

I am an immunologist who studies the fundamentals of immune responses to vaccination, so part of that responsibility falls on me.

Simply put, receiving these vaccines will likely make a whole lot of people feel crappy for a few days. That’s probably a good thing, and it’s a far better prospect than long-term illness or death.

Immunology’s ‘dirty little secret’

In 1989, immunologist Charles Janeway published an article summarizing the state of the field of immunology. Until that point, immunologists had accepted that immune responses were initiated when encountering something foreign – bacteria, viruses, and parasites – that was “non-self.”

Janeway suspected that there was more to the story, and famously laid out what he referred to as “the immunologist’s dirty little secret”: Your immune system doesn’t just respond just to foreign things. It responds to foreign things that it perceives to be dangerous.

Now, 30 years later, immunologists know that your immune system uses a complex set of sensors to understand not only whether or not something is foreign, but also what kind of threat, if any, a microbe might pose. It can tell the difference between viruses – like SARS-CoV-2 – and parasites, like tapeworms, and activate specialized arms of your immune system to deal with those specific threats accordingly. It can even monitor the level of tissue damage caused by an invader, and ramp up your immune response to match.

Sensing the type of threat posed by a microbe, and the level of intensity of that threat, allows your immune system to select the right set of responses, wield them precisely, and avoid the very real danger of immune overreaction.

Vaccine adjuvants bring the danger we need

Vaccines work by introducing a safe version of a pathogen to a patient’s immune system. Your immune system remembers its past encounters and responds more efficiently if it sees the same pathogen again. However, it generates memory only if the vaccine packs enough danger signals to kick off a solid immune response.

As a result, your immune system’s need to sense danger before responding is at once extremely important (imagine if it started attacking the thousands of species of friendly bacteria in your gut!) and highly problematic. The requirement for danger means that your immune system is programmed not to respond unless a clear threat is identified. It also means that if I’m developing a vaccine, I have to convince your immune system that the vaccine itself is a threat worth taking seriously.

This can be accomplished in a number of ways. One is to inject a weakened – what immunologists call attenuated – or even killed version of a pathogen. This approach has the benefit of looking almost identical to the “real” pathogen, triggering many of the same danger signals and often resulting in strong, long-term immunity, as is seen in polio vaccination. It can also be risky – if you haven’t weakened the pathogen enough and roll out the vaccine too fast, there is a possibility of unintentionally infecting a large number of vaccine recipients. In addition to this unacceptable human cost, the resulting loss of trust in vaccines could lead to additional suffering as fewer people take other, safer vaccines.

A safer approach is to use individual components of the pathogen, harmless by themselves but capable of training your immune system to recognize the real thing. However, these pieces of the pathogen don’t often contain the danger signals necessary to stimulate a strong memory response. As a result, they need to be supplemented with synthetic danger signals, which immunologists refer to as “adjuvants.”

Adjuvants are safe, but designed to inflame

To make vaccines more effective, whole labs have been dedicated to the testing and development of new adjuvants. All are designed with the same basic purpose – to kick the immune system into action in a way that maximizes the effectiveness and longevity of the response. In doing so, we maximize the number of people that will benefit from the vaccine and the length of time those people are protected.

To do this, we take advantage of the same sensors that your immune system uses to sense damage in an active infection. That means that while they will stimulate an effective immune response, they will do so by producing temporary inflammatory effects. At a cellular level, the vaccine triggers inflammation at the injection site. Blood vessels in the area become a little more “leaky” to help recruit immune cells into the muscle tissue, causing the area to become red and swell. All of this kicks off a full-blown immune response in a lymph node somewhere nearby that will play out over the course of weeks.

In terms of symptoms, this can result in redness and swelling at the injection site, stiffness and soreness in the muscle, tenderness and swelling of the local lymph nodes and, if the vaccine is potent enough, even fever (and that associated generally crappy feeling).

This is the balance of vaccine design – maximizing protection and benefits while minimizing their uncomfortable, but necessary, side effects. That’s not to say that serious side effects don’t occur – they do – but they are exceedingly rare. Two of the most discussed serious side effects, anaphalaxis (a severe allergic reaction) and Guillain-Barré Syndrome (nerve damage due to inflammation), occur at a frequency of less than 1 in 500,000 doses.

Side effects are normal.

Vaccination against SARS-CoV-2

Early data suggest that the mRNA vaccines in development against SARS-CoV-2 are highly effective – upwards of 90%. That means they are capable of stimulating robust immune responses, complete with sufficient danger signaling, in greater than nine out of 10 patients. That’s a high number under any circumstances, and suggests that these vaccines are potent.

So let’s be clear here. You should expect to feel sore at the injection site the day after you get vaccinated. You should expect some redness and swelling, and you might even expect to feel generally run down for a day or two post-vaccination. All of these things are normal, anticipated and even intended.

While the data aren’t finalized, more than 2% of the Moderna vaccine recipients experienced what they categorized as severe temporary side effects such as fatigue and headache. The percentage of people who experience any side effects will be higher. These are signs that the vaccine is doing what it was designed to do – train your immune system to respond against something it might otherwise ignore so that you’ll be protected later. It does not mean that the vaccine gave you COVID-19.

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It all comes down to this: Some time in the coming months, you will be given a simple choice to protect yourself, your loved ones and your community from a highly transmissible and deadly disease that results in long-term health consequences for a significant number of otherwise healthy people. It may cost you a few days of feeling sick.

Please choose wisely.The Conversation

Matthew Woodruff, Instructor, Lowance Center for Human Immunology, Emory University

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

Morrison government commits $1 billion over 12 years for new vaccine manufacturing supply



PMO, Author provided

Michelle Grattan, University of Canberra

The federal government has concluded a $1 billion agreement, funded over 12 years, with Seqirus to secure supply from a new high-tech manufacturing facility in Melbourne which would produce pandemic influenza vaccines as well as antivenoms.

This would boost Australia’s sovereignty when the country was faced with a future pandemic, and make for quick responses.

Seqirus, a subsidiary of CSL Ltd, will invest $800 million in the facility, which will be built at Tullamarine, near Melbourne airport. It will replace Seqirus’ facility in the inner Melbourne suburb of Parkville which is more than 60 years old. The Victorian government has supported the procurement of the land for the new operation.

Seqirus says the complex will be the only cell-based influenza vaccine manufacturing facility in the southern hemisphere, producing seasonal and pandemic flu vaccines, Seqirus’ proprietary adjuvant MF59 ®, Australian antivenoms and Q-Fever vaccine.

Work on construction will begin next year; the project will provide some 520 construction jobs. The facility is due to be fully operating by 2026, with the contract for supply of its products running to 2036.

The present agreement between the federal government and Seqirus is due to end in 2024-25.

Seqirus is presently the only company making influenza and Q fever vaccine in Australia, and the only one in the world making life-saving antivenom products against 11 poisonous Australian creatures, including snakes, marine creatures and spiders.

Scott Morrison said that “while we are rightly focused on both the health and economic challenges of COVID-19, we must also guard against future threats.

“This agreement cements Australia’s long-term sovereign medical capabilities, giving us the ability to develop vaccines when we need them.

“Just as major defence equipment must be ordered well in advance, this is an investment in our national health security against future pandemics,” he said.

Stressing the importance of domestic production capability, the government says when there is a global pandemic, countries with onshore capabilities have priority access to vaccines.

Health minister Greg Hunt said: “This new facility will guarantee Australian health security against pandemic influenza for the next two decades”.

Seqirus General Manager Stephen Marlow said: “While the facility is located in Australia, it will have a truly global role. Demand for flu vaccines continues to grow each year, in recognition of the importance of influenza vaccination programs. This investment will boost our capacity to ensure as many people as possible – right across the world – can access flu vaccines in the future.”

To deal with the present pandemic, the government has earlier announced $3.2 billion to secure access to over 134.8 million doses of potential COVID-19 vaccine candidates developed by the University of Oxford-Astra Zeneca and the University of Queensland, Pfizer-BioNTech and Novavax.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.

What do we know about the Novavax and Pfizer COVID vaccines that Australia just signed up for?



Shutterstock

Adam Taylor, Griffith University

The federal government’s announcement of agreements to supply vaccines from Novavax and Pfizer/BioNTech potentially increases the pool of COVID-19 vaccines Australians will be able to access.

These two vaccines are in addition to supply arrangements for vaccines from Oxford University/AstraZeneca and the University of Queensland/CSL, announced in September. Australia will also have access to vaccines via the World Health Organisation-backed COVAX initiative.

However, these arrangements depend on whether the vaccines are shown to be safe and effective in clinical trials, which are still ongoing. So what do we know about the two vaccines in this latest deal?




Read more:
Scott Morrison to announce two new COVID vaccine deals


What do we know about the Novavax vaccine?

The Novavax vaccine, NVX-CoV2373, contains purified pieces of the spike protein of SARS-CoV-2, the virus that causes COVID-19.

These proteins are administered with an adjuvant, a molecule that enhances the immune response. The idea is that when this vaccine is administered, the body recognises its contents as “foreign” and mounts a protective immune response.

Early clinical trials were performed in Australia. In the phase 1 clinical trials, the vaccine was generally well-tolerated and produced strong antibody responses, stronger than what we see in patients recovering from COVID-19.




Read more:
From adenoviruses to RNA: the pros and cons of different COVID vaccine technologies


In September, Novavax launched a phase 3 clinical trial in the United Kingdom. Further large-scale clinical trials are planned for other countries in late 2020 and early 2021.

If the Novavax vaccine is successful 40 million doses are expected to be available in Australia during 2021, with the option to buy a further 10 million.

What do we know about the Pfizer vaccine?

The vaccine developed by Pfizer, BNT162b2, is based on the genetic material mRNA (or messenger ribonucleic acid). Such mRNA vaccines carry a piece of genetic material that codes for viral proteins, or parts of them. Once inside your cells, the mRNA instructs your cells’ protein factories to make copies of these viral proteins. These then stimulate your immune system to mount a protective immune response.

Pfizer’s BNT162b2 vaccine codes for the virus’ full-length spike protein.

In early clinical trials, the vaccine was generally safe with no serious side-effects. The vaccine also produced a robust immune response after two doses.

Illustration of single-stranded RNA
Vaccines based on RNA use your cells’ protein factories to make viral protein, which stimulates your immune system.
Shutterstock

When older adults (65-85 years of age) were vaccinated, they produced a greater neutralising antibody response than seen in patients who contracted SARS-CoV-2 naturally.

Interestingly, BNT162b2 is one of the first COVID-19 vaccines to be tested in adolescents (12-18 years of age).

In July, Pfizer announced the launch of large-scale phase 2/3 trials. Trials are under way in several countries, including the United States, Germany, Argentina, Brazil and South Africa, involving 44,000 participants.

One of the challenges facing this vaccine is distribution, as it needs to be stored below -70℃. This is costly and makes transportation difficult, particularly in developing regions.

If BNT162b2 is successful, 10 million doses will be available in Australia from early 2021.




Read more:
Australia’s just signed up for a shot at 9 COVID-19 vaccines. Here’s what to expect


What happens next?

Both vaccines, if successful in clinical trials, will be manufactured outside Australia.

This will allay fears Australia might miss out on mRNA vaccines as the country does not have the technology and capacity to make these vaccines itself.

A successful COVID-19 vaccine will also need to navigate the rigorous assessment and approval processes of the Therapeutic Goods Administration for use in Australia.




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


Hedging our bets

It is unlikely all COVID-19 vaccines currently in development will be successful. We have already seen COVID-19 vaccine trials temporarily halted due to safety issues. And not all vaccines will provide a consistent level of immunity. Some vaccines may only provide immunity for limited periods of time and require a booster shot.

By investing in numerous front-running candidates, the Australian government’s strategy of not putting all its eggs in one basket is a wise one.

Investing in a range of vaccine technologies also has benefits, should more than one vaccine become available. This is because different vaccine technologies may be more effective or safe in different populations. This increases the likelihood all sections of society — young and old, with or without existing medical complications — could be targeted.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.

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


Archa Fox, University of Western Australia

The Australian government is in talks with pharmaceutical company Pfizer about potentially supplying its COVID-19 vaccine. The company has also secured preliminary clearance to apply for a type of fast-tracked regulatory approval for this vaccine.

But even if clinical trials showed this vaccine was safe and effective, Australia couldn’t make enough doses. We just don’t have the manufacturing capacity or technology in place.

So, has Australia missed a trick in not tooling up for these mRNA vaccines?

What are mRNA vaccines?

mRNA vaccines are coated molecules of mRNA, similar to DNA, that carry the instructions for making a viral protein.

After injection into muscle, the mRNA is taken up by cells. Ribosomes, the cell’s protein factories, read the mRNA instructions and make the viral protein. These new proteins are exported from cells and the rest of the immunisation process is identical to other vaccines: our immune system mounts a response by recognising the proteins as foreign and developing antibodies against them.

Infographic showing how mRNA vaccines work
mRNA vaccines work by delivering instructions to cells to make viral proteins. The body then makes these proteins, and the immune system recognises them and mounts an immune response.
Created with BioRender.com, Author provided

mRNA vaccines have several advantages. Their production process is almost identical for any possible mRNA. This means mRNA vaccines can be rapidly designed for new viruses or strains. This speed of design is why the COVID-19 mRNA vaccines are current frontrunners, and will probably be the first to get approval by the US Food and Drug Administration.

mRNA vaccines can be potentially quicker and cleaner to make than other vaccines. Unlike other types of vaccines made in living cells such as chicken eggs or genetically modified cell cultures, mRNA molecules can be made in an apparatus called a bioreactor. Some mRNA vaccines, such as Imperial College London’s vaccine now undergoing testing, are even self-replicating. This means the mRNA can copy itself inside our cells, so protein production lasts longer and, potentially, fewer doses are needed.

However, mRNA vaccines also have some disadvantages. As a new technology, no mRNA vaccine has ever been approved for clinical use. Unlike other vaccines, we do not have years of data on the safety of this type of vaccine to reassure the public.

They also need to be stored at very low temperatures. For example, Moderna’s needs to be kept at -20℃ and Pfizer’s at -70℃. At normal refrigerator temperatures of 2-8℃, they tend to last just a day or two. This means distribution may be difficult, especially in the developing world.

And crucially, most countries — including Australia — don’t have the mRNA manufacturing capability needed to make these vaccines at the required scale. So while the production of mRNA is cleaner, it may also be slowed by supply chain issues.

Which mRNA vaccines are the frontrunners?

There are six mRNA COVID-19 vaccines in clinical trials:

  • mRNA-1273 (Moderna, US) and BNT162 (Pfizer/BioNTech, Germany), both in phase 3 trials

  • CvnCoV (CureVac, Germany), phase 2

  • LUNAR-COV19 (Arcturus/Duke-NUS, Singapore), phase 1-2

  • COVAC1 (Imperial College, UK) and Covidvax (People’s Liberation Army Academy of Military Sciences/Walvax Biotech, China), both in phase 1.

The Moderna and CureVac candidates are both part of the COVAX initiative, a World Health Organisation-sponsored drive to boost vaccine research and give member countries a wider range of potential candidates.




Read more:
Australia’s just signed up for a shot at 9 COVID-19 vaccines. Here’s what to expect


As a COVAX member, Australia will have access to buy and distribute either of these vaccines if successful in clinical trials, and could also license the technology to make the vaccines domestically.

But Australia does not currently have the capacity to manufacture clinical-grade mRNA vaccines. Melbourne-headquartered global biotech firm CSL can make protein-based vaccines, and has expanded its capacity to include DNA/viral vaccines, but not mRNA.

CSIRO has facilities for making clinical-grade proteins for phase 1 and 2 clinical trials, but not vaccine-grade mRNA, and not at the scale needed for clinical trials, let alone for immunising the entire population.

Concerns raised

Australian scientists recently raised concerns about the lack of capacity for mRNA vaccine production.

In August, federal science and technology minister Karen Andrews, called on Australian businesses to come forward if they can help with vaccine production and distribution.

It is not publicly known whether any company responded indicating it could make mRNA vaccines.

With the federal government prepared to invest A$330 million in research for COVID vaccines and treatment, and mRNA vaccines clearly leading the global race, it’s possible some Australian biotech firms could pivot to mRNA production.

The CSL global product pipeline includes an mRNA vaccine against the flu in pre-clinical development. But CSL has issued no public statement about its capacity for Australian production of clinical-grade mRNA vaccines if this, or one of the COVID-19 mRNA candidate vaccines, requires a local supply. CSL has not declared any desire to establish mRNA manufacturing in Australia at this time.

So what should Australia do?

Australia’s first option will be to buy doses from overseas. But despite the COVAX deal it may still be at the end of a long queue, given the hundreds of millions of doses of Pfizer mRNA vaccine already pre-purchased by the United States, Japan and the European Union, and similar deals for these and other countries in negotiation with Moderna.

Compare this with Germany, where a planned rollout of the Pfizer vaccine to the elderly will start 24 hours after emergency approval, potentially as early as this month.

With the dose costing US$20-40 per person, even if we can secure doses, it could cost up to A$1 billion to immunise the Australian population if we buy the vaccine.

The second option is to to set up production of mRNA vaccines here, potentially led by a biotech firm with approval to make clinical-grade therapeutics. As a rough estimate, we calculate it could cost as little as A$100 million to make sufficient vaccine domestically. But it will mean a significant lag time, perhaps 12 months, to set up the infrastructure and train staff.

The lack of capacity to make mRNA is both a threat and an opportunity for the Australian biotechnology sector. Given the speed at which this technology has been applied to COVID-19, it would be useful to have this production capacity in Australia, so we can quickly respond to future pandemics.

Beyond vaccines, mRNA could be used for other promising therapies for cancer and other genetic diseases.

There is also the opportunity for creative innovation in this area. Tesla used its robotics capacity to create an mRNA synthesis platform for German biotech firm CureVac.

With investment by the federal government and willingness from the private sector, Australia could be part of this innovation wave. This technology would be useful for COVID-19 mRNA vaccines, future pandemics, and future medicines more broadly.


The author thanks the following researchers for contributions that helped inform this article: Damian Purcell, Peter Doherty Institute, University of Melbourne; Colin Pouton, Monash Institute of Pharmaceutical Sciences; Thomas Preiss, John Curtin School of Medical Research, ANU; Pall Thordarson, UNSW; and Nigel McMillan, Griffith University.The Conversation

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

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