Over 700 health experts are calling for urgent action to expand global production of COVID vaccines


Anupam Nath/AP

Deborah Gleeson, La Trobe University and Michael Toole, Burnet InstituteToday, we are joining over 700 health professionals and academics in sending an open letter to Prime Minister Scott Morrison urging him to take a leadership role in expanding the global production of COVID-19 vaccines and other medical tools to fight the pandemic.

The letter, signed by 207 doctors, 177 academics and 111 public health professionals, asks the government to help remove legal and technical barriers to increasing the production of COVID-19 vaccines, diagnostic tests, treatments and other equipment.

We argue there is more Australia — and other wealthy nations — can and should be doing to end the pandemic.

The need to act urgently

The COVID-19 pandemic is escalating sharply in the developing world. In addition to India’s spiralling infections, cases are surging across the globe in countries like Argentina, Uruguay, Sweden, France, Turkey, Mongolia, and Costa Rica.

The roll-out of vaccines must rapidly accelerate. Uncontained transmission will inevitably lead to the emergence of new variants that may be more infectious and resistant to vaccines.




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As of today, more than 1.06 billion vaccine doses have been administered worldwide. However, 37% of these doses have been given in the world’s 27 wealthiest countries. Those countries represent just 10.5% of the global population.

Meanwhile, countries making up the least wealthy 11% have received just 1.6% of the vaccine doses so far. At this pace, most of the world’s population will remain unprotected at least until 2023.

Vaccine shortage in India.
Vaccine shortages have been a frequent occurrence in India in recent weeks.
Rafiq Maqbool/AP

Monopolisation of vaccines

Two of the chief obstacles to vaccinating the world are the monopolisation of vaccines and the means of producing them. The world is relying on the pharmaceutical industry and market forces to solve the problems of inadequate supply and inequitable distribution — and this won’t work.

Rich countries have monopolised the world’s supply of vaccines by pre-purchasing doses in bulk. By November 2020, 7.5 billion doses had been reserved, half of these by rich countries making up only 14% of the global population.

Canada has more vaccines than it needs on order.
Countries like Canada have far more vaccines than they need on order.
Paul Chiasson/AP

Rich countries have also under-invested in COVAX, the global program for equitably distributing vaccines. COVAX needs an additional US$3.2 billion just to meet its target of vaccinating 20% of populations of participating countries.

Added to this, countries faced with large outbreaks have erected export restrictions to bolster their own supply of vaccines, excluding others.

This includes the European Union’s refusal to release 3.1 million doses to Australia this year. India has also restricted vaccine exports, resulting in delays in delivering 90 million doses to low-income countries.

The US, too, has been stockpiling its supplies, though the Biden administration announced this week it will now allow the export of raw materials needed to manufacture vaccines in India.

Monopolies on the means of producing vaccines

While the hoarding of vaccines is a concern, the monopolies on the rights to produce them is an even bigger problem.

The exclusive rights to manufacture COVID-19 vaccines are currently held by a small number of companies. These intellectual property rights are enshrined in the World Trade Organization Agreement on Trade-Related Aspects of Intellectual Property Rights, otherwise known as TRIPS.

Under TRIPS, WTO members must allow patents of at least 20 years for new pharmaceutical products, along with other types of intellectual property protection.




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TRIPS allows nations to invoke compulsory licensing of pharmaceutical products, which enables patented inventions to be produced without the consent of the patent owner in an emergency.

But compulsory licensing can only be applied on a product-by-product basis, and it only applies to patents, not the other types of knowledge and data needed to manufacture vaccines.

Countries also tend to face diplomatic and trade pressure not to enact such licenses. To our knowledge, no country has yet issued a compulsory licence for a COVID-19 vaccine.

Reliance on the pharmaceutical industry and market forces

So far, the world has placed its trust in the pharmaceutical industry and market forces to solve the problem, hoping vaccine makers would voluntarily enter into licensing arrangements with other manufacturers to increase supply.

But voluntary licensing has been little used to date. When it has been used, it has been done in an ad hoc and opaque way, with restrictive conditions.

AstraZeneca, Gamaleya/Sputnik V and Sinopharm are so far the only companies to implement voluntary licensing for COVID-19 vaccines. AstraZeneca, for instance, has licensed SK Bio in South Korea, the Serum Institute of India and CSL in Australia to manufacture the vaccine.




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Other companies’ reluctance to enter into these arrangements means available manufacturing capacity in Asia, Africa, and Latin America is not being used.

The pharmaceutical industry is heavily invested in the status quo. Pfizer and Moderna expect to generate US$15 billion and US$18.4 billion in revenue respectively in 2021, just based on existing supply agreements.

The People’s Vaccine Alliance estimates Pfizer, Johnson & Johnson and AstraZeneca have distributed US$26 billion to their shareholders in the form of dividends and stock buybacks in the past 12 months – enough to cover the cost of vaccinating 1.3 billion people.

A BioNTech production site in Germany
Pfizer/BioNTech’s goal is to produce 2.5 billion doses globally by the end of the year.
Michael Probst/AP

What Australia has done to help so far

Australia has been generous to date, providing AU$80 million to COVAX (specifically for low-income countries).

It has also pledged $523 million to the Regional Vaccine Access and Health Security Initiative, which provides health system support for vaccinations and $100 million to the Quad initiative by India, Japan, Australia and the US, which aims to distribute 1 billion doses in the Indo-Pacific region by 2022.

Australia has also provided 8,840 doses of AstraZeneca vaccine to PNG for frontline health workers and negotiated with the EU to free up 1 million of its own doses on order for PNG. Canberra has also pledged doses to Timor-Leste, Solomon Islands and Vanuatu.

These contributions are important stop-gaps to help address immediate needs. But they won’t go far enough on their own.

Further steps Australia needs to take

Increasing the global supply of vaccines will require governments to remove legal and technical barriers to their production.

To help remove legal barriers, the Australian government should support a proposal by India and South Africa in October 2020 to waive certain intellectual property rights for COVID-19 medical products.

This proposal, known as the “TRIPS Waiver”, is now supported by more than 100 of the WTO’s 164 member states. However, it has been blocked or stalled by the US, EU, Japan, Canada, and Australia.

Australia will have another chance to support it when it’s discussed at a TRIPS council meeting later this week.

To remove technical barriers, Australia must use its leverage to persuade pharmaceutical companies to share their knowledge and transfer technology to low and middle-income countries.

Australia should also endorse the COVID-19 Technology Access Pool (C-TAP), which was established last May by the World Health Organization but has so far been unused.

C-TAP relies on voluntary commitments by pharmaceutical companies. For it to work, governments need to provide incentives or require pharmaceutical companies to share their IP, data and know-how as a condition of public funding for research and development.

Over 700 health professionals and academics see the government’s leadership in these areas as a critical part of our pandemic response.

It’s time for Australia to act, and to encourage regional allies such as New Zealand, Japan, South Korea, and Singapore to do the same.The Conversation

Deborah Gleeson, Associate Professor in Public Health, La Trobe University and Michael Toole, Professor of International Health, Burnet Institute

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


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?




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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.




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The Conversation


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.

Flu vaccines are updated every year. We can learn from this process as we respond to COVID variants


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Sheena G. Sullivan, WHO Collaborating Centre for Reference and Research on Influenza and Kanta Subbarao, The Peter Doherty Institute for Infection and ImmunityWhile the future of the pandemic remains uncertain, we’ll probably have to live with COVID-19 for some time.

We face a range of possible scenarios. At the most optimistic end of the spectrum, new vaccines will protect against all current and future variants of concern. At the other extreme, we’ll see the frequent emergence and spread of new variants, against which existing vaccines will have limited effect.

It’s likely we’ll land somewhere in the middle.

Notably, although new variants do threaten the effectiveness of COVID-19 vaccines, decades of experience updating influenza vaccines can inform our global response.

Evolving variants

We’re still learning about how new viral variants affect vaccine effectiveness.

The B.1.1.7 variant, which emerged in the United Kingdom in late 2020, is more infectious and deadlier than the original strain of SARS-CoV-2 (the virus that causes COVID-19). Fortunately, though, preliminary data indicates COVID vaccines still work well against it (although this research hasn’t yet been peer-reviewed).

Meanwhile, a study published yesterday found the Oxford/AstraZeneca vaccine is ineffective against mild or moderate COVID-19 caused by the B.1.351 variant. This study was done in South Africa, where this variant emerged and is currently dominant.

Results of clinical trials of the Novavax and Johnson & Johnson vaccines indicated about 60% overall effectiveness in South Africa, according to the vaccine manufacturers. This is lower than the 70-90% reported in the United States and the UK.




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Notwithstanding differences in each country’s health systems and health status of their populations, which may explain some of the differences, this is a concerning trend.

Reassuringly, Johnson & Johnson reported 85% effectiveness against severe disease, regardless of country or variant. This suggests while some existing vaccines may not entirely prevent infection and mild illness caused by certain variants, they may still protect from severe illness and reduce the load on hospitals.

But if new variants continue to emerge, COVID vaccines may need to be reformulated regularly.

Several manufacturers have announced they’re already working on boosters designed to be more effective against the B.1.351 variant, which has now been detected in 48 countries.

An illustration of SARS-CoV-2, the virus that causes COVID-19.
New variants of SARS-CoV-2 pose a threat to vaccine effectiveness.
Shutterstock

Understanding the global spread of new variants

To develop updated vaccines that best respond to new variants, we need to understand the spread of the variants around the world. This is a big challenge.

To know which variant a person is infected with we need to sequence the viral genome (the genetic material of the virus), which can be expensive and time-consuming. While global access to diagnostic tests is improving, huge disparities in access to sequencing technology remain.

These disparities are reflected in information we have about currently circulating variants. Another variant of concern, P.1, shares some of the key mutations present in the B.1.351 variant. So it may present similar problems with vaccine effectiveness, although clinical trial data are lacking.

The P.1 variant was first identified in Tokyo in travellers from Brazil in January 2021. However, we now understand it’s been circulating in Brazil since early December 2020.

Around the world there have only been about 700 shared P.1 sequences, compared with more than 150,000 sequences of the B.1.1.7 variant. There are certainly far more than 700 cases of P.1, but resource constraints mean we’re not getting the full picture of how different variants are spreading.




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Further, while sequencing capacity has been massively scaled up during the pandemic, it cannot determine whether a mutation will change how the SARS-CoV-2 virus interacts with our immune system. This requires more lab work, called “antigenic characterisation”, with limited global capacity to undertake this specialised testing.

Patchy understanding of the nature and spread of new variants may lead manufacturers to focus on modifying their vaccines towards better-known variants, which at the moment are those found in more developed countries. These vaccines may be less effective in developing countries where less well-understood variants may predominate.

So we need ongoing, coordinated and global sharing of sequencing information and virus samples to track virus evolution and vaccine effectiveness.

Lessons from influenza surveillance

We’ve encountered similar challenges in the development of influenza vaccines, which are updated annually to ensure they remain effective against new strains.

Existing ‘flu surveillance has already been adapted to some degree for COVID. The Global Initiative on Sharing All Influenza Data, an online platform set up in 2008, has become the main tool used to share SARS-CoV-2 sequences.

In the case of influenza, we’ve seen a coordinated global response. The Global Influenza Surveillance and Response System, established in 1952, includes more than 140 laboratories across 114 countries. These labs share information on influenza viruses with five WHO Collaborating Centres, including genomic sequences, antigenic characterisation, and epidemiological data.

The WHO collaborating centres are then responsible for conducting further analysis to guide vaccine composition, inform regular global updates on circulating strains, and provide training and support to national laboratories.

Twice a year, WHO makes recommendations on vaccine composition for the following influenza season. These recommendations are not binding, but national regulatory agencies and manufacturers have consistently used them to develop ‘flu vaccines for more than 40 years.

A health-care worker dressed in PPE draws up a vaccine.
COVID vaccines are now rolling out around the world.
Shutterstock

A similar approach may prove useful for COVID-19. So far, manufacturers have made decisions about COVID-19 vaccine composition in consultation with national regulatory agencies. Developing a global framework to identify variants that warrant a vaccine update will allow manufacturers to focus on the technical aspects of vaccine development.

In turn, this will facilitate more rapid rollout of vaccines — and importantly, vaccines that are effective against variants circulating around the world, rather than only those affecting developed countries.

Some positives

Despite these challenges, current COVID-19 vaccines appear to provide strong protection against moderate to severe illness caused by most variants, and are likely to provide at least reasonable protection against others.

Also, SARS-CoV-2 mutates more slowly than influenza, meaning vaccines may need to be updated less frequently.

And finally, it will be easier and faster to modify new mRNA and vectored SARS-CoV-2 vaccines than traditional influenza vaccines.




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The Conversation


Sheena G. Sullivan, Epidemiologist, WHO Collaborating Centre for Reference and Research on Influenza and Kanta Subbarao, Professor, The Peter Doherty Institute for Infection and Immunity

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

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



from www.shutterstock.com

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.
www.shutterstock.com

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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Australia’s vaccine rollout will now start next month. Here’s what we’ll need


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.




Read more:
The Oxford/AstraZeneca vaccine is the first to publish peer-reviewed efficacy results. Here’s what they tell us — and what they don’t


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.




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


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.