Adrian Malloch

Race for a vaccine

In March, researchers around New Zealand dropped what they were doing to begin studying the novel coronavirus. Some realised that, if an effective immunisation is found, there will immediately be a long queue of nations jostling to buy billions of doses. So they resolved to make a vaccine themselves.

Written by       Photographed by Adrian Malloch

On April 2, James Dickson, a specialist in growing invisible proteins, received an envelope in the mail. Inside were two plastic vials, both of them smaller than his little finger. They were filled with a colourless liquid. At last, he had everything he needed to get started.

Dickson was alone in a squat Brutalist building at the University of Auckland, its long row of windows looking out among the branches of plane trees. The only sounds within were the hum of fridges and incubators.

He was prepared. He had colonies of E. coli sitting on ice in the freezer. He had embryonic human kidney cells in liquid nitrogen—the lab equivalent of protein-making factories. No time would be wasted.

James Dickson manufactures coronavirus proteins in his University of Auckland lab. He isolates them on acrylamide gels, checks they’re the right concentration, then sticks them in his pocket with some ice and walks to the medical school, where immunologist Nikki Moreland uses them to conduct antibody tests.

The task ahead of him was to create coronavirus proteins for an antibody test for COVID-19. Such a test would show whether someone had built up any immunity to the new coronavirus, and, if so, how much. It would show whether or not the person’s immune system had fought the virus—even if they hadn’t felt a thing. It would be a small step towards protecting ourselves from it.

Every virus sneaks into or picks the locks of your cells in different ways. Once inside, a virus takes over the cell’s machinery and starts making copies of itself. The novel coronavirus, which is named SARS-CoV-2, has a key for some of your cells—but not all. If you get a SARS-CoV-2 particle on the back of your hand, it can’t get in. Rub your eyes, and it’s a different story.

Picture the virus particle—that spiky ball. Think of those spikes as hands holding keys for cells in your nose, throat, eyes and lungs. The keys unlock your cells and let the whole particle in. Your immune system learns to keep a lookout for the spikes, and it creates antibodies dedicated to finding and neutralising them.

Before Dickson can grow spike proteins in human embryonic kidney cells, he has to check whether his culture of cells is in good nick. He uses an old-fashioned clicker to count them—like a ticket collector—to establish whether he has the right density of viable cells. “If you’ve got a really good healthy culture, that will be 99 per cent viable,” he says.

If Dickson was going to find those antibodies, first he’d need spikes—fake spikes—to trick a person’s immune system into mounting a defence. Then, immunologists would be able to tell if that person’s body had defended itself against the coronavirus before.

Those tiny vials contained the code Dickson needed to make his fake spikes. That colourless liquid contained plasmids—small loops of DNA that behave like a programmer’s code when inserted into cells. Put plasmids into human embryonic kidney cells, and those cells will start making spike proteins—in theory, that is. Dickson just had to figure out how to manufacture the spikes.

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Dickson might have been on his own in that lab, but he wasn’t working alone. Campbell Sheen at Callaghan Innovation had also received an envelope in the mail, and his contained plasmids from the United States.

With international supply chains fracturing, our science community was realising that New Zealand needed to build its own tests, treatments and vaccines.

The World Health Organization (WHO) is currently tracking the progress of 139 vaccine projects around the world. While the WHO is advocating for vaccines to be distributed equitably, based on need rather than nationality, there is no system in place for that to occur.

Once a COVID-19 vaccine is shown to be effective, there’ll be a queue for it almost eight billion people long, not to mention a global shortage of vaccine-production factories, warns Graham Le Gros, research director of the Malaghan Institute.

On April 24, Le Gros and others called for vaccine research funding, pointing out that New Zealand already has production capacity due to the number of animal vaccines we manufacture. (Auckland facility BioCell Corporation is now locked in to manufacture a potential COVID-19 vaccine created by British biotechnology company Stabilitech.)

On May 26, the government announced $10 million in funding for local vaccine research, and set aside $5 million for production.

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Making a vaccine involves understanding how the human immune system deals with SARS-CoV-2—and that’s something we have only a vague idea of. Part of the problem is that the virus hasn’t been around long enough for us to watch how the body reacts to it over the long term.

“Even globally, the longest data that we have is really [from] January until now,” says immunologist Nikki Moreland from the University of Auckland. “It’s going to be some time before we have a good understanding of antibody persistance.”

Dickson worked for two and a half months straight at this desk in the lab.

Immunologists need to know exactly which antibodies are involved in neutralising the virus, and how they do it. “And how long does that neutralising activity last?”

The immune system has different departments that perform different roles—let’s say it has an army, navy and air force—and the response it mounts to each disease is unique. Over time, scientists learn to read the signs that someone has immunity to a particular pathogen. Perhaps it’s the navy that always responds, and it sends its submarines, but leaves the battleships at home. Perhaps it needs  four submarines to win the battle, so if you’ve only got three, it’s clear to scientists that you won’t be immune to that disease.

“So we don’t know that for COVID-19 yet,” says Moreland. We don’t know which branch of our body’s immune system is involved in neutralising the virus, and we don’t have a record of what the body requires to neutralise it, whether it’s four tanks and a helicopter, or two bomb disposal units and a Penguin missile.

And, in the body as in the real world, we don’t always hold on to our defences. For some illnesses, the immune system may decide that keeping four submarines around isn’t important, and disband them.

So, the big question is whether humans will have long-term immunity to SARS-CoV-2. A recent study by Duke-NUS Medical School in Singapore of people who had the SARS virus in 2003 may hint at an answer. Researchers tested whether those people still had antibodies for the original SARS virus, 17 years after infection—and they did, says Moreland. “So that gives us some hope—but of course there’s never been another wave of SARS, so in terms of the actual real-world experience of whether they’re truly protected from reinfection, we don’t know that. But certainly, in a laboratory, they look like they are.”

Moreland’s next task is to look at the antibodies they’ve detected so far in more detail. Which parts of the spike protein, exactly, are those antibodies attacking?

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Researchers don’t usually start building vaccines without understanding exactly what the human immune system does in response to a disease. But that’s exactly what’s been happening around the world, and in New Zealand, in response to COVID-19.

Dickson’s fake spikes could be a building block for one type of vaccine. It could be used to provoke an immune response, or it could be attached to a synthetic virus particle to make it look even more like the real thing. The theory goes that the more like the real virus a vaccination looks, the better your immune system arms itself. “That’s hypothetically where you’d take it in terms of vaccine development,” he says.

One project, based at the University of Otago’s high-security physical containment lab, aims to use the real virus—rather than a fake one—to create a vaccine. (To work in the lab, scientists must suit up like old-fashioned deep-sea divers, with respirators that pump their suits full of fresh air.)

Plasmids arrived from the United States in small plastic vials, like those pictured.

Deactivating live viruses is a common mechanism for creating vaccines. Scientists figure out how to kill the part of the virus responsible for infection, while leaving the rest of it intact (usually by poisoning the virus with formaldehyde). The human body still recognises the virus as a threat—in the same way you might have an adrenaline response to an anaesthetised tiger. Virologist and University of Otago professor Miguel Quiñones-Mateu says his team’s deactivated viruses are ready for testing in mice, and he’s closely following the progress of a similar vaccine being developed in China.

New Zealand’s vaccine research projects are some way behind others internationally. Several overseas have already progressed to the stage of being tested in humans—the longest and trickiest part of vaccine development.

Dickson doesn’t work with the virus itself—only synthetic versions of its spiky outer coating. He replicates plasmids in flasks of E. coli, which shake in an incubator at 37 degrees Celsius, the temperature of a human body.

However, if those efforts fail, the world still needs a vaccine. New Zealand will be months closer to the goal than if we hadn’t started. Nobody knows what the answer will look like, or where it will come from.

For now, extra spike proteins chill at negative 80 degrees Celsius, SARS-CoV-2 grows under maximum security in a Dunedin lab, and in laboratories around the country, scientists are searching for the answer to a question we are barely beginning to understand.

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