The story behind the blistering speed of COVID-19 vaccine development

This column is an instalment in our series Apocalypse Then, in which cultural historian Ainsley Hawthorn examines the issues of COVID-19 through the lens of the past.

Past pandemics can bring our experiences with COVID-19 into focus, by reassuring us that we're far from the first people to face a serious outbreak or by showing us how similarly our ancestors reacted to the threat of illness.

It's also impossible to understand the efficiency of our medical response to COVID, especially the speed of vaccine development, without looking to the past.

Before COVID-19, the fastest a vaccine had ever been developed was four years. Researcher Maurice Hilleman swabbed his sick daughter's throat in 1963 and had a mumps vaccine in hand by 1967. By comparison, a recently approved vaccine for Ebola took over 20 years to refine.

It's hardly surprising, then, that the blistering pace of the COVID-19 vaccine creation raised eyebrows. The World Health Organization declared COVID-19 a pandemic on March 11, 2020, and Health Canada approved Pfizer's vaccine against the virus in early December, less than nine months later.

That breakneck turnaround time had some people wondering whether researchers sped up the process by taking shortcuts. But they didn't need to. A past epidemic had given them a huge head start.

In 2012, a new disease emerged in Saudi Arabia: Middle East respiratory syndrome, often called MERS. Although only a handful of cases were identified that year, later outbreaks in Saudi Arabia in 2014 and South Korea in 2015 led to hundreds of deaths.

Like COVID-19, MERS is caused by a coronavirus — the two share about 50 per cent of their genetic sequence. Although MERS doesn't spread as easily as COVID, it's significantly more deadly. Nearly 35 per cent of people infected with MERS die of respiratory distress, blood clots or organ failure.

Jason McLellan, a molecular bioscientist based at the University of Texas at Austin, had been working on vaccine development for several years by the time MERS appeared on the epidemiological landscape, and he wondered whether the severe new illness could be prevented through vaccination.

To help on the project, he recruited graduate student Daniel Wrapp and postdoctoral researcher Nianshuang Wang, who, for his doctoral thesis at Tsinghua University, had worked out the structure of MERS' spike protein.

A crown of spikes

Coronaviruses are named for the crown (or corona) of spikes that cover their outer surfaces. McLellan and his team wanted to find a way to manufacture MERS' spike protein by itself, without the virus attached to it. If they could do that, they theorized, they could teach the body's immune system to recognize and attack the spike without ever having to expose the body to the deadly virus itself.

They faced a serious challenge. Coronavirus spikes change shape when they interact with human cells, making them too unstable to reproduce. After years of making one tiny genetic tweak after another, the team finally found the right combination of modifications to lock MERS' spike protein into a consistent shape, a tremendous step toward creating a vaccine.

Much to their surprise, though, none of the top scientific journals were interested in their findings. It took them a full year to publish their results.

Other researchers just didn't think MERS and other coronaviruses were that important at the time.

By then, MERS had slowed to only a couple hundred cases per year, and the overall risk from coronaviruses seemed low. Most health officials expected the next global pandemic to come in the form of a new strain of influenza.

All that changed at the beginning of 2020. In the first few days of January, McLellan was snowboarding with his family when his phone rang. It was a collaborator giving him a heads-up that a strange new coronavirus was circulating in the city of Wuhan.

Trials started 2 months after genome was sequenced

Given the seriousness of MERS and SARS before it, they both knew that a coronavirus outbreak could spell trouble. McLellan alerted his team members that they would be jumping into analyzing this new virus as soon as they had more information.

A few days later, Chinese researchers published the genome of the virus online, and McLellan's lab, like researchers around the world, went to work.

It was Jan. 10, the day before China confirmed its first death from COVID-19. It would be another two weeks before Wuhan entered lockdown and two months before the WHO declared a pandemic.

Armed with the techniques they'd already developed, it took McLellan and his team only an hour to figure out how to stabilize the new virus' spike protein. Soon they began shipping their fixed version of the protein to other labs around the world.

It would be used as the basis for the Moderna, Pfizer-BioNTech, Johnson & Johnson, and Novavax vaccines.

Each of these vaccines works by delivering a blueprint of COVID's spike protein into our bodies, instructing our own cells to create copies of the spike. Recognizing these spikes as interlopers, our immune systems produce antibodies to neutralize them, antibodies that will be standing by to attack COVID-19 itself if we're ever infected.

Moderna was the first of these vaccines to enter human trials, on March 16, 2020, just 65 days after the sequencing of the coronavirus genome.

That record-breaking speed was possible only because of technologies that had already been perfected. The vaccines took not one but seven years to develop.

Thanks to MERS, McLellan and his lab were prepared to rapidly respond to a new coronavirus. If the pandemic had been caused by another type of pathogen, like an arenavirus, we might still be waiting for a vaccine.

History, in this case, was on our side.

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