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Source: The Conversation – UK – By Rob Reddick, Commissioning Editor, COVID-19

Since the early days of the pandemic, attention has focused on producing a vaccine for COVID-19. With one, it’s hoped it will be able to suppress the virus without relying purely on economically challenging control measures. Without one, the world will probably have to live with COVID-19 as an endemic disease. It’s unlikely the coronavirus will naturally burn itself out.

With so much at stake, it’s not surprising that COVID-19 vaccines have become both a public and political obsession. The good news is that making one is possible: the virus has the right characteristics to be fended off with a vaccine, and the economic incentive exists to get one (or indeed several) developed.

But we need to be patient. Creating a new medicine requires a large amount of thought and scrutiny to make sure what’s produced is safe and effective. Researchers must be careful not to allow the pressure and allure of creating a vaccine quickly to undermine the integrity of their work. The upshot may be that we don’t have a highly effective vaccine against COVID-19 for some time.

Here, authors from across The Conversation outline what we know so far. Drawing upon their expertise, they explain how a COVID-19 vaccine will work, the progress a leading vaccine (developed by the University of Oxford with AstraZeneca) is making, and what challenges there will be to manufacturing and rolling a vaccine out when ready.

How will vaccines work for COVID-19?
How the spike protein is produced
The benefits of different designs
Why boosters may be needed
What determines how we respond to vaccines
Why vaccines provide strong immunity
How to use a vaccine when it’s available

How is the Oxford vaccine being developed, tested and approved?
The many steps of vaccine development
The results of phase 1 and phase 2 trials
How the phase 3 trial will work
Why testing was paused – and why we shouldn’t be alarmed
Why vaccine makers need to be more open
Why we need to know what’s in placebos

How will the vaccine be made and rolled out?
How to prepare enough vaccines for the whole world
How tobacco could play a role in producing a vaccine
Why vaccines need to be kept cold
Will rich countries buy up the supply when vaccines are available?
How to stop rich countries from depriving poorer ones
Who should get a vaccine first?

How do you counter resistance and scepticism?
Vaccine hesitancy is nothing new
Are anti-vaxxers that big a problem?
How the far right is exploiting the pandemic
How to build trust in vaccines

How will vaccines work for COVID-19?

Producing the spike protein

Although the way the body interacts with SARS-CoV-2 isn’t fully understood, there’s one particular part of the virus that’s thought to trigger an immune response – the spike protein, which sticks up on the virus’s surface. Therefore, the two leading COVID-19 vaccines both focus on getting the body to produce these key spike proteins, to train the immune system to recognise them and destroy any viral particles that exhibit them in the future.

SARS-CoV-2, with its spike proteins shown in red. US Centers for Disease Control and Prevention/Wikimedia Commons

The pros and cons of different designs

The leading vaccines both work by delivering a piece of the coronavirus’s genetic material into cells, which instructs the cell to make copies of the spike protein. As Suresh Mahalingam and Adam Taylor explain, one (Moderna’s) makes the delivery using a molecule called messenger RNA, the other (AstraZeneca’s) using a harmless adenovirus. These cutting-edge vaccine designs have their pros and cons, as do traditional methods.

Boosters may be needed

The strongest immune responses, says Sarah Pitt, come from vaccines that contain a live version of what they’re trying to protect against. Because there’s so much we don’t know about SARS-CoV-2, putting a live version of the virus into a vaccine can be risky. Safer methods – such as getting the body to make just the virus’s spike proteins, or delivering a dead version of the virus – will lead to a weaker response that fades over time. But boosters can top this up.

if boosters are required, manufacturing sufficient doses and delivering them will become an even greater challenge. SiphiIwe Sibeko/EPA

What governs how we respond to vaccines?

A vaccine’s design isn’t the only factor that determines how strong our immune response is. As Menno van Zelm and Paul Gill show, there are four other variables that make each person’s response to a vaccine unique: their age, their genes, lifestyle factors and what previous infections they have been exposed to. It may be that not everyone gets long-lasting immunity from a vaccine.

Why vaccines provide strong immunity

If well-designed, a vaccine can provide better immunity than natural infection, says Maitreyi Shivkumar. This is because vaccines can focus the immune system on targeting recognisable parts of the pathogen (for example the spike protein), can kickstart a stronger response using ingredients called adjuvants, and can be delivered to key parts of the body where an immune response is needed most. For COVID-19, this could be the nose.

Nasally delivered vaccines are already in use for some diseases, such as flu. Douglas Jordan, MA/CDC

How to use a vaccine when it’s available

Scientists think between 50% and 70% of people need to be resistant to the coronavirus to stop it spreading. Using a vaccine to rapidly make that many people immune might be difficult, says Adam Kleczkowski. Vaccines are rarely 100% effective, and hesitancy and potential side effects may make a quick, mass roll-out unrealistic. A better strategy might be to target people most at risk together with those likely to infect many others.

How is the Oxford vaccine being developed, tested and approved?

The many steps of vaccine development

Vaccine development is quicker now than it ever has been, explain Samantha Vanderslott, Andrew Pollard and Tonia Thomas. Researchers can use knowledge from previous vaccines, and in an outbreak more resources are made available. Nevertheless, it’s still a lengthy process, involving research on the virus, testing in animals and clinical trials in humans. Once approved, millions of doses then need to be produced.

Phase 1 and phase 2 trials are successful

After showing promise in animals, the University of Oxford’s vaccine moved onto human testing – known as clinical trials, which are split into three phases. Here, Rebecca Ashfield outlines the joint phase 1 and 2 trial that the vaccine passed through to check that it was safe and elicited an immune response, and explains how the vaccine actually uses a separate virus – a chimpanzee adenovirus – to deliver its content into cells.

Production of the Oxford/AstraZeneca vaccine in Latin America is taking place in Argentina; part of the phase 3 trial is being run in Brazil. EPA-EFE

How the phase 3 trial works

Earlier trial phases showed that the vaccine stimulated the immune system, as expected. But the million-dollar question is whether this actually protects against COVID-19. Finding out means giving the vaccine to thousands of people who might be exposed to the coronavirus and seeing whether they get sick. As Ashfield and Pedro Folegatti show, this requires running vaccination programmes in countries across the world.

Testing was paused – and that’s OK

In September, the phase 3 trial of the Oxford vaccine was paused after a patient fell ill with a possible adverse reaction. Understandably this caused dismay, but it shouldn’t have, says Simon Kolstoe. Pauses like this are common, as independent moderators are needed to assess exactly what has happened. Often illnesses in trials are unrelated to what’s being tested. But even if they are, that’s exactly what we want these tests to show.

In the US arm of the trial, one-third of participants are receiving a saline injection as a control. DonyaHHI/Shutterstock

But vaccine makers need to be more open

AstraZeneca didn’t publicly reveal what caused the pause but did

ref. Coronavirus vaccine: what we know so far – a comprehensive guide by academic experts –

MIL OSI – Global Reports