In the 2011 movie “Contagion,” which recently surged in popularity as people learned about the worldwide COVID-19 outbreak, a scientist proves her experimental vaccine is effective by testing it on herself. Things aren’t quite so easy in the real world. That’s why, even though the first subjects are already receiving an experimental coronavirus vaccine, and researchers and the federal government are eager to move as fast as possible, it could still be a year or longer before a vaccine is ready to deliver to the general population.
In some ways, researchers had a head start on developing an inoculation for the new coronavirus, says Lee Riley, a professor of infectious disease at the School of Public Health at the University of California, Berkeley. A lot of research went into possible vaccines for the earlier SARS and MERS outbreaks, which were caused by other types of coronaviruses. “It wasn’t that much of a leap” to start work on a vaccine for the virus that causes COVID-19, Riley says.
The study that just began at the Kaiser Permanente Washington Health Research Institute in Seattle is what’s called a phase I trial. It will include just 45 volunteers, who will get the experimental vaccine in various doses. The vaccine doesn’t contain the coronavirus itself. Rather, it will train the subjects’ immune systems to attack the “spike protein” coating the virus.
The main purpose of a phase I trial is to test safety, explains Kathryn Edwards, a pediatrician and vaccinologist at Vanderbilt University. The volunteers will closely monitor their health after getting their shots: Do they have a rash? Fever? Headache? If they sneeze, Edwards says, researchers want to know about it.
Additionally, scientists will add live coronavirus to samples of the volunteers’ blood to see whether they’re making antibodies that can fight it. If the blood from vaccinated people doesn’t put up any resistance against the virus, researchers will know the vaccine had failed.
If all goes well, the Food and Drug Administration will give the go-ahead for a phase II trial. These generally involve several hundred people, all healthy adults. Using a larger number of subjects lets researchers look for less common reactions to a vaccine. It also lets them make sure that everyone’s blood shows an immune response to the virus after they’re vaccinated. (That’s one reason the “Contagion” vaccine isn’t realistic — a single scientist injecting herself can’t prove the vaccine is safe or effective for others. And unlike the movie scientist, no one in a trial for a new coronavirus vaccine would be intentionally exposed to the virus.)
Finally comes a phase III trial. That’s when researchers give a vaccine to a large number of people and wait to see whether they’re less likely than unvaccinated people to come down with the illness. Some new vaccines never reach this stage, Edwards says, because an outbreak has died down in the meantime. This happened with some experimental Ebola vaccines.
Even in the best case — a vaccine that turns out to be safe and effective — the steps in the process add up to many months. Researchers must recruit people for each new phase. Then they have to wait a few weeks after injecting subjects to check their immune response. After researchers compile the data on all of their volunteers’ immune responses and any negative reactions, they present the data to the FDA and get approval for the next phase. And even if approval came more quickly than usual in the case of COVID-19, a phase III trial would still need to follow people for long enough to judge whether the vaccine has protected them. Rushing things could result in a vaccine that’s harmful; there have been cases in which people who received a vaccine actually got sicker when they encountered the virus itself.
Given all the steps that are required even before a vaccine can be manufactured in large quantities, Edwards says she thinks it was “really a very realistic expectation” when Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, said that it could take 18 months to have a COVID-19 vaccine ready.
Meanwhile, other researchers are exploring ways to treat people who are already sick. Some studies of antiviral drugs, including an experimental drug called remdesivir, are underway now. But even if there were a good drug to fight the coronavirus, patients would need to get it early. Once the infection has harmed their lungs badly enough, an antiviral drug likely won’t help. And developing treatments for COVID-19 could take even longer than developing a vaccine, Riley says: “Vaccines offer better hope.”
The ideal solution, Riley says, would be a universal vaccine against all coronaviruses. “We may be able to develop such a vaccine with the technologies we now have,” he says. Rather than banking solely on that, however, the country needs to put a lot more money into both the prevention and treatment of infectious diseases. “This is a wake-up call,” Riley says.
Elizabeth Preston is a science writer in the Boston area.