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Normal text size Larger text size Very large text size Barely six weeks after the first recorded death from the new coronavirus in Wuhan, researchers in Australia began testing a potential vaccine on animals. A factory in Melbourne has created small doses of the vaccine for testing. If it keeps animals safe from the virus, it will be tested on humans. And the CSIRO have just finished developing an "animal model" – a ferret infected with the virus – which gives scientists an insight into how COVID-19 progresses and provides a basis for testing ways to stop it. 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? The virus responsible for COVID-19, isolated from the first Australian coronavirus case and captured in this colorised transmission electron micrograph image. Credit:CSIRO


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 a lengthy process, 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 SARS (Severe Acute Respiratory Syndrome) and MERS (Middle Eastern Respiratory Syndrome) and then Ebola and Zika viruses emerge, killing thousands and terrifying the world, scientists 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, it was launched in 2017 and is headquartered in Norway. The coalition’s plan: to build "platform vaccines" that could be instantly adapted to new viruses when they emerged. The challenge: they would need to invent vaccines unlike any in use right now. 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. 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. At the moment, there are three common types of vaccine Sub-unit vaccines contain a single piece of a virus in a soup of chemicals that cause the body to generate antibodies. Examples: hepatitis B, shingles, HPV, some flu shots. Live-attenuated vaccines contain a live virus that has been subtly weakened so that it still infects cells but does not make people sick. This allows the body to generate antibodies. Examples: measles, mumps, rubella. Inactivated vaccines contain a virus that has been killed. Our immune system recognises the dead virus and produces antibodies. Examples: rabies, hepatitis A, some flu shots. 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’s 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.


Professor Paul Young, left, Dr Keith Chappell and Dr Dan Watterson have developed a new vaccine technology. Credit:University of Queensland 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. A 3D map of the virus's spike protein which the team is attempting to copy. Credit:Science The potential solution is 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. Loading 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. Professor George Lovrecz and Mylinh La at CSIRO's manufacturing facility for a pilot coronavirus vaccine in Clayton, Melbourne. Credit:Scott McNaughton You’ve got a potential vaccine. Then what? On February 21 the team’s vaccine draft was sent to the CSIRO’s manufacturing facility in the Melbourne suburb of Clayton, and manufacturing of a pilot dose began. The facility houses a 200-litre fermenting vat that will be filled with a “soup” of Chinese hamster ovary cells – the best cells for the task – in a nutritious goo. The clamped protein DNA sequence from the University of Queensland lab has been fed 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. “We hope... 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.” Professor George Lovrecz with a fermenter where vaccine proteins will be grown. Credit:Scott McNaughton 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. Using that sample, they have now been able to show that ferrets can also get infected with COVID-19. They are now studying the course of that infection – how the animal gets sick, which cells the virus targets, and how the immune system responds. Knowing the course of the illness is important because it allows a proper comparison to be made. The sick ferrets can be compared to ferrets given a test vaccine to see if it is truly protective. 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. Loading 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 in 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. Mylinh La at CSIRO's vaccine manufacturing facility. Credit:Scott Mc Naughton