Vaccine development takes time. Earlier this spring, we learned that the previous record for vaccine development was four years from sample to approval, and that we might not see a COVID vaccine for years, if at all. But here we are, barely one year past the discovery of the novel coronavirus, and we already have a vaccine authorized in the U.S. for emergency use, and several more emerging from phase 3 trials or already in emergency use in other countries.
“Was it rushed?” is the question I keep hearing. Personally, I wouldn’t say that. I’ve been reading the trial data, listening in on FDA and CDC meetings, and carefully following the reactions of experts. It truly does not seem that corners have been cut. Instead, the speed of this vaccine is due to a combination of luck, good planning, and unprecedented coordination between researchers, manufacturers, and regulators.
Let’s break down some of the steps in the vaccines’ development so we can see where the time went. I’ll focus on the mRNA vaccines that are currently the front runners in the U.S.: the FDA recently granted an emergency use authorization for the Pfizer/BioNTech vaccine, and may grant another for the Moderna version as soon as next week. The advantages I describe here also benefited many of the other vaccine candidates, both here and abroad.
The basic research on this type of virus stretches back years
Before COVID, there was SARS. The initially-mysterious respiratory illness sickened people in China in late 2002 and began to spread worldwide before eventually fizzling out thanks to careful quarantines and international cooperation.
SARS was also caused by a coronavirus. The COVID virus is so similar to it that it was named like a movie sequel: the SARS virus is SARS-CoV, the new coronavirus is SARS-CoV-2.
The SARS outbreak spurred research on deadly, contagious coronaviruses. Another illness in this family, MERS, popped up in the Middle East in 2012. So while the COVID virus is new, research on stopping or preventing a pandemic caused by a coronavirus has at least an 18-year history.
Basic molecular biology research has also become more advanced over the years. Scientists are now so fast at sequencing viral RNA that the coronavirus’s sequence was published on January 10, 2020, less than a month after the virus was first discovered.
mRNA vaccines also have a long history
There has never been an mRNA vaccine licensed for human use; the Pfizer/BioNTech vaccine, if it reaches full approval as planned, will be the first. But researchers didn’t build the technology from scratch this year.
The idea of using RNA (the virus’s genetic material, without any other parts of the virus) in a vaccine dates from the early 1990s, so there’s been almost 30 years of research on this technology. According to a review published in 2018, mRNA vaccines had already been used to elicit immunity against influenza, Zika, and rabies.
Along the way, scientists ran into problems—like the possibility that mRNA vaccines could cause autoimmune conditions—and also figured out how to solve them. Chemically modifying the mRNA and encasing it in tiny bubbles made it safe. The 2018 review states: “Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans.” Even then, this way of developing vaccines was praised for its “capacity for rapid development.”
Knowing how to build a given type of vaccine can really accelerate building the actual vaccine. In that sense, we’ve actually already seen vaccines be developed in less than a year: just look at flu shots. Every year’s flu shot is different from the year before, but it’s not built from scratch. Vaccine makers already have labs and factories set up to make flu vaccines, and each year they just plug in the specific influenza strains that they’ll need.
Remember how the virus’s genome was published in January? Moderna told reporters that their labs were already set up to make mRNA vaccines, so that once they downloaded that data, they were able to whip up a vaccine in two days.
Vaccine trials normally involve a lot of waiting
Several vaccine trials started this spring, around the time the U.S. was just starting to grapple with the idea of lockdown. Huge amounts of money poured in, from various countries’ governments and from other funding bodies and donors. Everyone was ready to get shit done.
Pharma companies wanted to make vaccines ASAP, and regulators in the U.S. and other countries wanted to be able to approve vaccines ASAP. Normally in a trial there is a lot of waiting: waiting for funding, for paperwork, for review boards to meet and discuss things at a glacial pace. Once a trial has the green light, you have to recruit volunteers.
In ordinary times, a vaccine would have taken months to years to get through all this red tape. But this aspect of the timeline is something that people can accelerate just by wanting to. The FDA, for example, aims to process most applications for a new drug or vaccine within 10 months. “Expedited” review is six months. But for the first COVID vaccine? They called an emergency meeting and were ready to approve it within three weeks.
The pandemic getting worse actually sped up the trials
The vaccine trials weren’t scheduled to last a certain number of weeks or months; rather, the companies and regulators determined ahead of time that they would continue until a certain number of COVID cases showed up in volunteers.
The trials do not intentionally expose people to the virus; that’s considered unethical. So all you have to do is vaccinate half your participants, and then wait. If there are low numbers of disease cases in the area, it may not be possible to finish the trial; that has happened before. But in the case of the Pfizer/BioNTech and Moderna trials, and many others, the pandemic actually picked up speed while phase 3 trials were being done. Cases quickly accumulated, and the study could be ended and results analyzed sooner than anyone had predicted.
Everything happened in parallel
Normally, you do each step of developing a vaccine before you do the next. There’s no point in manufacturing all those little bottles of liquid and printing the labels if you don’t know yet whether the vaccine will work, or whether the FDA will even agree that it’s worth approving.
But here, everything happened at once. The vaccine companies began manufacturing doses as fast as they could, even before trials were finished. Government agencies, including the FDA and CDC and a whole alphabet of committees and related agencies, began discussing the potential vaccines even before they had a specific application in front of them.
For example, the Advisory Committee on Immunization Practices, which recommends vaccines to the CDC, met several times this year to plan out very meta topics, like how they would make decisions about making decisions about any potential vaccines. Does COVID pose enough of a risk to the American population that a vaccine is worthwhile at all? (Yes.) On what basis should groups of people be prioritized? (They have a whole framework that balances science, ethics, and practicality.) This committee normally meets in its own time after the FDA has approved a vaccine; this time, they called an emergency meeting so they could finalize their recommendations less than 24 hours after the FDA had granted emergency authorization.
Fast, but not rushed
It seems that what we ask, when we wonder if the vaccine was rushed, is whether the same vaccine would have been approved if the politics of a pandemic were not surrounding it. But it’s difficult to separate the politics of a pandemic from the science of it.
Doctors, regulators and individual human beings all have to consider risks and benefits when deciding whether to use a medical intervention. Overwhelmingly, the FDA and CDC’s advisors agreed that the known and potential benefits of the vaccine outweigh the known and potential risks. If COVID were a less deadly disease, the balance would have shifted and the unknowns might have loomed larger.
Imagine a less-deadly COVID; a common cold, perhaps. If there were a vaccine for the common cold, would it have sailed through approval with just two months of follow-up and an open question about whether it poses a risk to people with severe allergies? I doubt it; I bet the FDA would have told them to go back and do a longer trial and gather more data to address some of the uncertainties.
But stalling too long is, itself, a harm. The CDC’s computer models have shown that the way to save the most lives with a vaccine is not down to the details, like giving it to this group or that group first, but simply to get the vaccine to everyone as soon as possible.
In the name of transparency, the FDA published their Emergency Use Authorization memorandum about the Pfizer/BioNTech vaccine recently. You can look over all the scientific data and the summaries of it, as well as the information it contains about the manufacturing facilities and the plans for collecting safety data even after the vaccine is rolled out.
And so that’s where we are. The vaccine looks safe and effective, so far. Nobody will be forced to take it, so if you’d like to wait and see if unknown side effects start showing up, you’re welcome to sit back and watch. Personally, if I lived or worked in a nursing home, I would get the shot in a heartbeat. Since I’ll likely be pretty far back in the line, I’m watching with interest to see if we learn any more about this vaccine, or about the others, as time goes on.