Coronavirus outbreak: How the COVID-19 vaccine is being made

Scientists around the world are working at lightning speed to make a COVID-19 vaccine – and Australian experts are bringing breakthrough technology to the effort. How do you make a vaccine and what's new about this Australian innovation?

Barely six weeks after the first recorded death from the new coronavirus in Wuhan, researchers in Australia will begin testing a potential vaccine on animals.

A factory in Melbourne is expected to begin producing small doses of the vaccine within weeks for further testing. If it keeps animals safe from the virus, it will be tested on humans.

The extraordinary plan – to develop a vaccine for a virus we barely understand, at breakneck pace – is being led by a team of scientists at the University of Queensland, with support from other teams around the country.

If their efforts succeed, not only will they have a powerful weapon to stop the spread of coronavirus but they will also revolutionise vaccine technology, potentially leading to jabs for a range of other lethal conditions.

How do you make a vaccine for a new disease? What are these new “molecular clamp” vaccines and how do they differ from our current inoculations? How do you make one so quickly? And how likely is it to work?

 

What is the plan for developing a COVID-19 vaccine?

Vaccines are among our best tools for preventing infection. In the developed world they have helped largely stamp out crippling diseases such as polio, diphtheria and rubella.

But historically, making a vaccine has been long, arduous, frustrating and often unsuccessful. It takes about 10 years to bring a vaccine all the way from research through to approval – and that’s if the vaccine works. Many more end up as failed experiments.

After watching first SARS (Severe Acute Respiratory Syndrome) and MERS (Middle Eastern Respiratory Syndrome) and then Ebola and Zika emerge, killing thousands and terrifying the world, scientists around the world decided a new approach was needed – one that could quickly make vaccines in response to emerging threats. Known as the Coalition for Epidemic Preparedness Innovation (CEPI), it was launched in 2017 and is headquartered in Norway.

The coalition’s plan: to build "platform vaccines" that can be instantly adapted to new viruses when they emerge. The challenge: they would need to invent vaccines unlike any in use right now.

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The CEPI coalition wants to go from isolating this coronavirus to testing a vaccine for it within 16 weeks – so it would be ready for wide distribution within 12 to 18 months. In the world of vaccines, that’s lightning fast.

Its first major test has come faster than anyone could have expected. Having emerged from a live animal market in the Chinese city of Wuhan, COVID-19 has rapidly turned into a global menace. As of February 19, 75,199 people have fallen ill and 2012 have died.

The Doherty Institute for Infection and Immunity in Melbourne captured a sample of the virus from the first person in Australia diagnosed with the disease. They placed the virus inside a flask filled with monkey kidney cells, monitoring the flask via a video camera.

On the video below, you can’t see the virus – it’s too small. The cells sit quietly in a bath. Slowly at first but then more and more quickly they start turning black, until the entire dish is filled with death.

Above: In this timelapse image, the virus cannot be seen but evidence of its presence can be. The healthy cells start off transparent; as they become infected, they turn black. Source: Dr Julian Druce VIDRL, The Doherty Institute

How do vaccines work? Why do we need a new type?

All vaccines work by taking advantage of your immune system’s innate defences. A vaccine contains a part or all of a virus, treated in such a way that it won’t make you sick. Your immune system recognises the virus as a foreign invader and then makes different antibodies to destroy it.

Every virus has a different shape. To kill it, your body needs to produce antibodies that are exactly the right shape to stick to the virus. Imagine puzzle pieces slotting together – but when they connect, the virus dies.

The CEPI coalition has three vaccines for coronavirus in development around the world (with the hope that at least one works). Two of them, being developed by pharmaceutical companies working with CEPI, Inovio and Moderna, are of a type known as “DNA” vaccines. The other, being developed in Australia, is a “molecular clamp” vaccine. Other companies in China and Russia are independently working on their own vaccines outside of the coalition.

One key thing the CEPI coalition is doing differently is to not use the virus in making a vaccine. In a new outbreak, getting a live sample of a virus takes too long. Instead, they are using its genetic code, which can be obtained as soon as an outbreak starts.

Scientists analyse a virus’ genetic code and identify a section that contains the blueprint for a small part of the virus. If you inject that DNA into human cells, the human cells will read it and start printing off small parts of the virus. Your immune system spots these virus fragments and makes antibodies to kill them – giving you immunity.

“That is the simplest vaccine we can make, and we can make them very quickly. But they are often not terribly effective,” says Professor Eric Gowans, a DNA vaccine expert formerly based at the University of Adelaide.

The molecular clamp vaccine being developed for CEPI at the University of Queensland is entirely different.

 

What is a molecular clamp vaccine?

Molecular clamp technology was invented about seven years ago by three University of Queensland scientists: Dr Keith Chappell, Dr Daniel Watterson and Professor Paul Young.

Funded by CEPI, they had hoped to spend the next few years developing their innovation; instead, they have been thrust into the heart of the fight against COVID-19.

The virus’ genetic sequence was released by China on January 11. Within 24 hours, the team had picked the part of the virus they wanted to target and ordered the materials to get started.

“We did not need the virus itself. All we needed was the sequence,” says Professor Young.

Viruses have a single goal: to get inside a human cell, where they can reproduce. To do this, the coronavirus is covered in “spike” proteins, which are coiled up like tiny springs.

Spike proteins are designed to bind to a human cell and uncoil, blowing a hole in the cell wall that lets the virus in.

Our immune system works by recognising that protein and making antibodies to kill it. Specifically, you want your antibodies to recognise and kill the coiled shape of the spike proteins – killing the coronavirus before it gets a chance to penetrate your cells.

If you want to give someone immunity without infecting them, the obvious thing to do is cut off a spike protein and stick it in a vaccine.

But it’s not that simple.

Put a coiled spike protein – unconnected to the surface of the virus –  in a vaccine and inject it, and the spike proteins will automatically uncoil inside the body.

Rather than making antibodies to fight the coiled protein on the surface of COVID-19, the body will make antibodies that match the shape of the uncoiled protein. If full coronavirus comes along, those antibodies won’t kill it.

The potential solution: molecular clamps.

These clamps are tiny pieces of protein that fix the spike protein in its coiled shape. “It locks the protein into the shape that’s seen on the virus,” says Professor Young.

Trapped in that shape, the protein is ripe for investigation by the immune system. This encourages the immune system to generate not one but many different antibodies to attack the virus, meaning your immunity is stronger, says molecular biologist Upulie Divisekera at the University of Auckland.

The coronavirus is also mutating, much as the flu mutates to escape our immune system. By generating a whole range of different antibodies you should be able to get a broad immune response that can still handle a mutated coronavirus, Divisekera says.

By the second week of February, the University of Queensland team had a batch of their clamped proteins. They have picked out several shapes that look like they will encourage strong immune response. By the third week of February, they expect to start testing on animals in the lab.

You’ve got a potential vaccine. Then what?

The University of Queensland team will spend two more precious weeks further tweaking the shape to get it just right and then send it for small-scale manufacture – and broader testing.

This will be done at the CSIRO’s manufacturing facility in the Melbourne suburb of Clayton. The facility houses a 200-litre fermenting vat which will be filled with a “soup” of Chinese hamster ovary cells – the best cells for the task – in a nutritious goo.

The CSIRO team will be supplied with the clamped protein DNA sequence from the University of Queensland lab, and they will feed that DNA into the fermenters. The cells will absorb the DNA and copy the instructions it contains, manufacturing litres and litres of the clamped protein. That will then be extracted, purified and placed in a vaccine.

The facility is already practising manufacturing a dummy vaccine for MERS, a closely related virus.

“We hope – and that’s why we’re practising on MERS – we can give the purified material within four weeks for toxicology studies,” said Professor George Lovrecz, research team leader at CSIRO’s manufacturing division.

“I believe they are very, very close to having the first vaccine candidate ready.”

How would the vaccine be tested?

Before you can hand the vaccine to humans, you need to test it’s safe and effective. At the CSIRO’s highly secure laboratory in Geelong, south-west of Melbourne, those tests are already being prepared.

Scientists at the lab have used the virus sample from the Doherty Institute to grow their own vats of coronavirus. When Clayton has finished a batch of test vaccine, it will be administered to small animals – probably ferrets – at the Geelong lab. The ferrets will then be exposed to the coronavirus.

The results will be known quickly. If the ferrets stay healthy, human trials can begin. If they don’t, it is back to the drawing board.

"We feel we could be doing testing [in animals] by mid-March," says Dr Rob Grenfell, director of health and biosecurity at the CSIRO.

Will it work?

The technology works – on paper. Scientists are very excited. Several told us the University of Queensland’s vaccine had at least a 50-50 chance of succeeding.

But the road to scientific discovery is paved with failure. Two-thirds of new drugs that work on animals simply don’t work in humans.

So the scientists at CEPI estimate they would need to test as many as 21 different vaccines to have a good chance of one working.

Here's the thing, though: they only need to succeed once.

This article Coronavirus outbreak: How the COVID-19 vaccine is being made was originally published in The Sydney Morning Herald.

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