Above: illustration by Matthew Roharik/Getty Images

In November 2019, a team from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, visited Moderna, Inc.’s manufacturing plant in Norwood, Massachusetts. The biotech firm was planning to expand the newly opened facility to accommodate its vaccine development work, and CEO Stéphane Bancel (MBA 2000, AMP 170) welcomed input on the design from the government’s infectious disease experts. For two years, Moderna had been working closely with the NIH to create a vaccine for Middle East respiratory syndrome (MERS), a coronavirus that causes fever, cough, and shortness of breath. The spread of MERS had been limited since its emergence in Saudi Arabia in 2012, with only about 2,500 total cases globally, but one in three infections resulted in death.

Through its work on MERS and other vaccines in its pipeline, Moderna had refined its development process—which begins with an analysis of a virus’s messenger RNA (mRNA)—and it had improved its production capabilities. Two months earlier, when he'd met NIAID Director Dr. Anthony Fauci at the NIH, Bancel said that, faced with an unknown virus, Moderna could create a vaccine for clinical testing in just 60 days. That was three times faster than any vaccine candidate had ever been produced. Fauci didn't believe him.

An idea emerged to test Bancel’s record-breaking claims: a mock pandemic. The NIH would provide Moderna with a computer model of a virus the company had not seen before and start the timer. Bancel was eager for the chance to show off the company’s agility. The organizations settled on the spring of 2020 for this “outbreak”; the first quarter of the year was just too busy.

The whole world knows what happened next. A few days into the hectic new year, news broke of an unusual cluster of pneumonia cases in Wuhan, China. On January 11, 2020, the Chinese government posted the genetic sequence of what it had identified as a novel coronavirus. Moderna had its test, and the clock was ticking.

In two days, the company developed a computer model of a potential mRNA-based vaccine. Twenty-five days after that, it produced the first dose of a treatment it hoped would protect against a disease that did not yet have a name. On February 24, after 17 days of analysis and sterility testing, Moderna shipped the first batch to the NIH for clinical testing. The company had moved from concept to clinical-trial-ready in a record-breaking 42 days.

Moderna is just one of scores of research teams worldwide currently shepherding vaccine candidates through development and testing with unprecedented speed. Each is focused on producing a safe and effective vaccine. But the ultimate goal is even more ambitious than bringing an end to the current pandemic as quickly as possible. True success, say those involved, will be building the infrastructure necessary to prevent the next one.

The day before this novel coronavirus made headlines, the vaccine sector was a pretty sleepy space. Interest in vaccine development and production had been on the decline for decades. In the 1960s—the triumphant years after Jonas Salk discovered the first polio vaccine—there were 26 pharmaceutical companies worldwide producing inoculations at scale; by the 1980s, that number had fallen to 18, and by 2015, it was just four.

“Vaccines went out of fashion,” says HBS professor Gary Pisano, who studies the intersection of business and science. “There was a sense among investors that they were boring.” (Pisano consults for pharmaceutical and biotech companies and has a financial stake in Moderna.) There was a dollars-and-cents logic to this, since the big rewards that can be had in the pharmaceutical industry come with big financial risks. “There’s really no other industry where you have to deal with such profound and persistent uncertainty,” Pisano says.

But vaccines don’t really fit the same business model as high-volume therapeutic drugs; they have an even higher bar for safety and effectiveness, because unlike most other drugs they are administered to healthy populations. And while that’s a potentially enormous market, most vaccines are used only once or twice in a person’s lifetime—a far different business opportunity than the one presented by drugs that treat chronic diseases. In addition, governments are the major purchaser of many vaccinations, effectively capping prices, and vaccines are particularly vulnerable to accusations of price gouging and calls for generic alternatives.

The few big companies still investing in vaccines saw their fortunes take an upward turn in the mid-2010s, as countries with growing economies, like China, expanded immunization programs, and policymakers in established economies looked to control healthcare costs through better prevention. For instance, in 2014 the United States’ Centers for Disease Control and Prevention recommended that all adults over 65 receive a dose of Prevnar 13, a Pfizer product that protects against 13 of the approximately 90 types of pneumococcal bacteria that can cause pneumonia; it had previously only been recommended for children. (The recommendation was later softened when it became clear that vaccinating children naturally led to fewer cases in older adults.) But few believed that the underlying fundamentals of the vaccine market had changed. For most companies, the financial risk remained too high to justify the potential reward—a situation that too often led to dangerous vaccine shortages.

It was at this moment that Moderna turned its attention to vaccines. The company had been founded in 2010 with the intention of using a new method of mRNA modification to develop therapeutic treatments. mRNA directs protein development in cells, and Moderna’s founders and other researchers believed introducing synthetic mRNA into the body could spark the production or expression of proteins to heal cardiac tissue, improve renal function, and treat several rare genetic diseases. Early efforts were not wholly successful, but mRNA experiments had one consistent result: They triggered an immune response.

Bancel, who joined the firm in 2011, and his partners saw opportunity in the vaccine market so many others had written off. They believed Moderna’s technology offered two advantages. First, the company had been focused on creating not a single drug, but a platform for analyzing proteins and producing synthetic mRNA. That same process could be used to analyze the proteins on a virus and develop a synthetic virus mRNA to encourage the body to produce antibodies. In this way, Bancel hoped, Moderna would be able to develop vaccines more quickly and inexpensively than other companies and create a diverse portfolio of products. Second, the production of mRNA was more efficient than many methods of vaccine manufacturing because the actual proteins were created inside the human body. The company launched its first vaccine trial for a strain of avian influenza in 2015.

If developing vaccines for widespread and endemic diseases has long been considered a financially unattractive proposition, doing so for emerging strains posed an additional challenge: There was no guarantee that the disease would still be prevalent by the time a vaccine became available. This had been the case with severe acute respiratory syndrome (SARS), a dangerous coronavirus identified in the Guangdong province of southern China in 2002. For six months, the disease threatened to become a pandemic. Travel restrictions were put in place, quarantine orders issued, and vaccine development fast-tracked. SARS sickened about 8,000 people and killed about 800 in 32 countries, but by mid-2003, the disease had all but disappeared. On the science side, further research was hampered by a lack of test subjects; on the investor side, there was no longer a ready customer base for a SARS vaccine. None ever came to market.

In the early days of January 2020, before anyone fully understood how widespread the novel coronavirus outbreak would become, Moderna announced its first vaccine candidate to move into Phase II clinical trials—a prophylactic against cytomegalovirus, a common virus that has little effect on healthy adults but severe consequences for infants and those with compromised immune systems. Bancel expected the company to spend the year much as it had spent 2019, expanding and advancing its development pipeline. Moderna had five additional vaccines in Phase 1 testing and two more in preclinical development. It was a portfolio that looked promising to investors. In late 2018, the company’s IPO had broken biotech records with a valuation of about $7.5 billion—but Moderna was still several years away from producing any of its products at commercial scale.

For many of the companies now in the hunt for a vaccine, the choice to scrap 2020 business plans and focus on the emerging virus was not self-evident. Even as the human cost of COVID-19 was becoming increasingly apparent, the economics of the sector made fighting the virus a less-than-obvious business choice. The market size for a vaccine was unknown, and the paths for financing such research—which could have a price tag in the billions for each effort—were unclear. At Moderna, Bancel and his leadership team weighed that risk with the reward: the opportunity to prove the value of its mRNA platform, bring its first commercial vaccine to market three or four years faster than anticipated, and make history.

As of August 31, there were more than 165 efforts to find a vaccine underway around the world. Of those, 36 were in human testing and two, touted by China and Russia, had been approved for limited use, though experts cautioned that both vaccines needed further testing. Most attention has been focused on Moderna and the NIH, which launched a Phase 3 trial on July 27 with plans to enroll 30,000 people in the United States, and two large pharmaceutical companies: AstraZeneca and the University of Oxford had a vaccine based on a chimpanzee adenovirus in Phase 3 trials in Brazil and South Africa, while US-based Pfizer, in collaboration with Germany’s BioNTech and the Chinese drug maker Fosun Pharma, were recruiting another 30,000 volunteers in the United States and several other countries to evaluate its own mRNA-based solution in a Phase 2/3 trial.

“We’re not racing against each other,” says Bancel of the multitude of vaccine candidates. “We’re racing the virus.”

In the quest for a coronavirus vaccine, science is only part of the story. This pandemic will not end with the development of a safe, effective inoculation. That inoculation also needs to be approved, manufactured, and distributed globally. The world doesn’t need one dose, or 1,000 doses, or even the 500 million doses produced annually to combat the flu. It needs billions of doses, in every country. So while the public waits anxiously for updates on clinical trials, those behind the scenes are focused on more mundane but equally vital concerns: regulatory approval, which varies from country to country, manufacturing capacity, supply chains, and money, lots of money.

As the head of the United Kingdom’s new Vaccine Taskforce, Kate Bingham (MBA 1991) has a bird's-eye view of the whole process. A life science venture capitalist with SV Health Investors, Bingham was appointed in May to lead the government group, which reports to the prime minister, after the tragic scope of the pandemic had become clear. Her job—not that different from the role of a VC—is to build and lead a team to identify promising vaccine candidates and shepherd them from development to deployment. On any given day Bingham’s attention is as focused on clinical trial enrollment as it is on, say, cold-chain distribution (some of the vaccines under consideration must be maintained at –122 degrees Fahrenheit).

As with any startup, money was the first obstacle Bingham needed to solve but, in this case, it was the easiest to overcome. Nonprofit organizations and governments around the world have poured billions into vaccine efforts. By midsummer, Moderna, for instance, had received $955 million in US government funding; it raised an additional $1.3 billion on the capital market.

That kind of money buys speed: In normal times, a vaccine developer concerned about financial risk would move through phased clinical trials in sequence, with a pause between each for evaluation and planning. But when time is of the essence and money a secondary concern, as in the COVID-19 research, those phases overlap as the pace of the trials is dictated by the science rather than the investment risks. Companies with vaccines in testing are already stockpiling doses for distribution. If the testing shows the product to be unsafe or ineffective, all those doses will be destroyed—but if the product is approved, distribution can begin immediately.

Another key item on the UK Vaccine Taskforce to-do list is capacity. The task force has purchased dedicated manufacturing facilities to produce COVID-19 vaccines, including one that until recently manufactured veterinary drugs, and it is helping to procure other necessities that are in high demand and short supply, such as glass vials and stoppers. The global goal is to produce 2 billion doses of each approved vaccine—even those in the race to produce a vaccine hope that more than one will be successful—in 2021.

Bingham’s task force has also been working closely with regulators to streamline the review process. As with clinical trial testing, the plan is to run the regulatory process in parallel with research. To save time and labor, the task force has developed turn-key trial protocols and invested in consistent assays for analyzing vaccine effectiveness, and the UK’s centralized health system provides the task force with efficient recruitment capabilities for trials.

And the group is looking even further ahead. Planning is already underway, with options including six national vaccination centers in the United Kingdom in addition to making the vaccines available at neighborhood polling places. In fact, Bingham is so focused on problem-solving for every step of vaccine distribution that she’s already thinking about the backlash against the eagerly awaited inoculation: “Considering the anti-vax movement, how do you persuade people to take the vaccine?” she asks. The concern is particularly relevant given the compressed timeline of vaccine development. “Everybody says, ‘It normally takes 10 years to develop a vaccine. How come you are doing it in a year?’” Bingham says. Her answer: unprecedented funding and unheard-of cooperation.

It’s a vital lesson, she says. One of the six teams that comprise the UK Vaccine Taskforce is dedicated to what Bingham calls “industrial legacy,” or how the choices the world makes now will contribute to long-term pandemic preparedness.

There are two things nearly everyone involved in the race for a vaccine seems to agree on.

First: There will be a vaccine.

No one can yet say when it will arrive. Some, like Bancel, predict that a vaccine approved for emergency use could be administered to hospital workers as early as this fall. Others, like Bingham, are quick to point out that even after vaccines are approved, distribution will be targeted, with those at greatest risk receiving them first, a process that will take months, even years. The young and healthy may never receive one, Bingham says, since the benefit may never outweigh the risk for those least likely to contract the disease, even though they may be the source of disease transmission.

No one can yet say what form the vaccine will take, either. It could be a single dose, or two phased doses, or an annual dose. It might be made from an inactivated form of the virus, modified mRNA or DNA, an adenovirus, or one of a half-dozen other methods currently being tested. And no one can yet say how effective it will be. The MMR shot, which protects against measles, mumps, and rubella, is 97 percent effective when children are given two doses. Last year’s flu shot was 45 percent effective. Dr. Anthony Fauci has suggested that a COVID-19 vaccine that is 70 percent effective would be considered a win. It would end the pandemic, though the world would continue to face outbreaks.

Second: There will be another virus with the potential to become a pandemic.

On this topic, too, no one is certain as to when it will happen or what form it will take. But those whose days are spent working toward a COVID-19 vaccine have some ideas for how to revamp the vaccine sector in anticipation.

For Bingham, building factories that can quickly pivot to meet pandemic-time needs is essential. She also believes that the high level of engagement between vaccine developers and regulators, which has allowed the review to proceed without delay, will be a model for future pandemic planning.

For Bancel, preliminary research on 20 major viruses that infectious disease experts have identified as potential pandemic sources is also key. He credits the two years of work that Moderna did on MERS—also a coronavirus—for allowing the company to move so quickly on the initial steps of the COVID-19 vaccine. The type of research he envisions would require government investment, he says, but not much. “You’re talking $10, $20 million dollars per vaccine preclinical,” he points out. “It’s not a lot of money on the scale of a country. Governments spend billions of dollars every year on nuclear weapons they are hoping to never use, so what about spending a couple of billion dollars to build plants, teams, and scientific work and projects to equip ourselves so this never happens again?”

COVID’s severity has catalyzed an unprecedented response when it comes to swiftly moving through the phases of vaccine development. For comparison, the timeline below contrasts a typical pre-COVID vaccine with that of Moderna’s trajectory, which has been accelerated by unprecedented levels of funding and cooperation as well as the company’s use of mRNA technology.

Typically, the vaccine development process pauses between each phase for evaluation and planning. When time is of the essence and money a secondary concern, as with COVID-19 research, those phases overlap, as shown above. Investments are made, for instance, in Phase 2 testing before Phase 1 data is available. If the vaccine candidate proves safe, Phase 2 can start immediately. If it fails the safety test, the money is lost. Likewise, companies are already manufacturing and stockpiling doses of vaccines. If a vaccine proves unsafe or ineffective, all those doses will be destroyed—which seems like a waste, until you consider that beginning production the day a vaccine is approved would add six months or more to distribution efforts.

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