In early January, McLellan was snowboarding with his family in Utah when he got a call from Graham. He was calling about the disease circulating in Wuhan: “It looks like this is a coronavirus,” Graham said. “Are you ready to put everything together and race on this?”
“Yes,” McLellan replied. “We’re ready.”
On January 10, one day before China announced its first death from the new disease—at that point it was known to have sickened just 41 people—a consortium of researchers published a draft sequence of the genome of the new virus. Labs across the world got to work. In Texas, it was Friday night, but McLellan and his team didn’t wait. SARS-CoV-2 was a new version of a familiar problem; they could apply the stabilizing mutations they’d been developing right away. McLellan messaged Daniel Wrapp, a grad student, on WhatsApp. The next morning, Wrapp and Kizzmekia Corbett, the scientific lead of the Vaccine Research Center team that studies coronaviruses, got to work using mutations their colleague Nianshuang Wang had already identified. Within an hour or two, they had a genetic sequence for a stabilized version of the new virus’s spike protein.
As their MERS collaboration continued, scientists at the Vaccine Research Center and Moderna had been exploring whether it would be possible, if a viral epidemic were to break out, to work together and use Moderna’s mRNA platform to make a rapid vaccine. Within a day of getting the sequence of the new virus, they decided to try. In those early days, the outbreak was still widely expected to be contained. Rather than a world-changing pathogen, says Moderna’s president, Stephen Hoge, the virus at first seemed like an interesting opportunity to test the potential of their collaboration and their technology.
The scientists adapted their previous work to target the specific spike of SARS-CoV-2. “Plug and play,” Corbett calls it. First, they had to choose which protein to express. The teams considered whether to use the wild form of the new virus’s spike protein or the stabilized, pre-fusion one, but they agreed that the latter was more likely to make the best antigen. (“The point of a vaccine is to do better than natural infection,” Corbett would later explain on CNN. “The point of a vaccine is to create an immune response that is very potent, so, high-level immunity for an extended period of time.”)
Then it was up to Moderna to decide how to encode that protein in mRNA—a problem with an overwhelming number of possible solutions, but one that the company had prepared for, by using machine learning to train algorithms to pick sequences best able to express a given protein. From those possibilities, they manually selected the most promising. (They also planned backups, in case their selection wasn’t supported by new data, but the alternatives didn’t prove necessary.) By January 13, the scientists had finalized the genetic sequence of a vaccine they called mRNA-1273, which would enter Neal Browning’s arm two months later. The process was incredibly fast, says Jordan, but only if you ignored all the work that came before. “You’re able to do this in a few weeks, but it’s a few weeks plus 10 years.”
Even with the head start, beginning the trials so quickly required a sprint. The news about the virus’s spread, and its effects on those it infected, kept getting scarier. It was soon clear that more was riding on the vaccine than anyone had initially realized. Within two weeks, scientists at Moderna, without being asked, were staying late, working weekends. Corbett’s team started growing spike proteins and stocking freezers with vials. They immunized mice with the vaccine, then tested their blood for antibodies. A clinical batch was ready by February 7, tested and shipped by February 24, and green-lit for human testing by March 4. (It was a coincidence that the human trials began in what had, by March, become the first hot spot in the US; Kaiser Permanente Washington Health Research Institute had been selected to conduct them in late January.) There was never a singular moment, says Hoge, when he realized the researchers had begun an 18-month marathon. Instead, “it felt like every day, can you run faster, can you run faster, can you run faster?”
Even after trials began in record time, that remained a key question. Were there other ways to speed up development? Usually, a vaccine moves through phases sequentially, proving itself before its producers are willing to invest in the next step. By the end of January, CEPI selected mRNA-1273, along with three other vaccine candidates, for emergency funding, allowing the researchers to start preparing extra vaccine material for future phases of testing. In April the US government approved nearly half a billion dollars for Moderna from the Biomedical Advanced Research and Development Authority (Barda)—money that would allow for more staff, more equipment, and more space to produce large quantities of a vaccine that was still months from being proven (or disproven) to work. (Barda also supported other companies, including Johnson & Johnson and Sanofi.) Instead of the normal sequential process, Jordan says, Moderna was “shingling”: preparing everything it could, as soon as it could, in the hope that all the work wouldn’t turn out to be wasted. “This is not normal times,” explained Hoge. The company is now preparing to produce a million doses a month by the end of this year, and tens of millions of doses a month in early 2021. All of a vaccine that has not yet entered an efficacy trial.
On the same day Neal Browning got his shot of Moderna’s first-out-of-the-gate vaccine, another candidate from the company CanSino Biologics in China became the second SARS-CoV-2 vaccine to officially move into human trials. Within a few weeks, three other vaccines—two from Chinese labs and a DNA-based one pioneered by the Pennsylvania-based company Inovio—also got the green light. The list of projects for vaccines targeting SARS-CoV-2 expanded and expanded and then expanded some more; as of mid-April, the WHO listed 78 active efforts and 37 others for which statuses weren’t public. CanSino announced that one of its vaccines was ready to move onto efficacy testing.