The race for a COVID-19 vaccine is unprecedented: 198 potential vaccines are now in development, and that development is happening faster than it ever has in history. Moderna, for example, finalized its vaccine just days after Chinese researchers released the genetic sequence of the new coronavirus in January. Two months later, the first volunteer was dosed with the vaccine. Last week, the company published positive Phase I trial results showing that the vaccine seems safe and generates an immune response; days later, Oxford University researchers published similarly promising results.
But until larger trials are complete, it won’t be clear whether any of the vaccines actually prevent COVID-19—or how long that protection will last. Historically, most vaccines in development have failed. For a world that has poured billions into developing the new coronavirus vaccines, with manufacturing beginning even before trials end, what would it mean if none of the vaccines succeed?
The risk of failure is still a real possibility. “This is extremely early data,” says Raphael Viscidi, a virologist and professor of pediatrics and oncology at Johns Hopkins School of Medicine. We know that the vaccines that have progressed furthest can cause the body to generate neutralizing antibodies against the virus. But we don’t yet know if those antibodies will prevent disease, and many other questions remain. “The most important is the duration of that response,” he says. “That’s always an issue with the vaccine: How long will the desired response last?” Natural immunity against other coronaviruses, like OC43, one cause of the common cold, is short-lived. If a vaccine has to be given repeatedly, especially if it’s more than once a year, it becomes more impractical for it to be widely used. (Even if the vaccine is effective, the growing anti-vax sentiment is another challenge; if too many people refuse to get vaccinated, we won’t reach herd immunity.)
The first trials also only tested the vaccines on a small number of people. “We do not know what is happening in the older people,” says Sanjay Mishra, a researcher at the Vanderbilt Vaccine Center. “And you’ve seen how skewed the effect of the COVID-19 is—it affects older people most.” It’s possible that older people may have a weaker antibody response, for example. There may also be other challenges that become apparent over time. Some failed vaccines for other diseases have had a “disease enhancement” effect, meaning they actually make the immune system more susceptible to the disease. Viscidi says that there’s also a risk that a vaccine might interact in unexpected ways with other coronaviruses, such as the common cold, SARS, or MERS; if a vaccine helps prevent COVID-19 but worsens another virus, that would obviously be a problem. He argues that the process of testing may need to last longer than the current ambitious timelines.
Oxford, which has partnered with AstraZeneca, has said that initial doses of its vaccine could be ready as early as September. But trials could take longer than expected. Another challenge is that enough people in a trial have to be exposed to the virus to determine a clear difference between the placebo and the vaccine, while warning volunteers that none of them should knowingly expose themselves to the virus. In the meantime—or if the vaccines aren’t effective enough in the final analysis—the world will have to turn to other ways to deal with the disease.
“Plan B for that situation is plan A for today,” says Jonathan Quick, managing director of the Pandemic Response, Preparedness, and Prevention Health Initiative at the Rockefeller Foundation. That means better adoption of best practices such as social distancing, wearing masks, and avoiding large crowds. It will mean more development of therapeutics that help manage the symptoms and more deployment of the ones that are being tested now, from plasma antibody treatments to drugs like dexamethasone, which can help some of the most critically ill patients and, by extension, help overwhelmed hospitals have the capacity to help more patients. “One of the distinguishing features of COVID versus, for example, the flu, is that COVID is the only infectious disease that we’ve ever seen crash intensive care units, and part of it is the long length of stay,” he says.
It also means a massive scale-up of testing and contact tracing, something else that could have helped prevent deaths and economic destruction if it had been put in place earlier. The Rockefeller Foundation recently published a report with recommendations for national testing and tracing. That plan includes faster testing, so patients can get results and a clear action plan while they’re still in a doctor’s office (in some cases, results now are delayed by as long as two weeks, rendering them useless for preventing the spread of the virus). It also involves clear protocols for screening at high-risk locations such as nursing homes or meatpacking plants, investment in R&D for new tests, and much clearer communication nationally about when people need to be tested.
All of this needs to happen even if vaccines are successful. “We ought to be planning to be living with this for at least another year, year and a half, even if we do get a good vaccine,” Quick says. “It may well be the good vaccine won’t be the best vaccine, and scale-up is an issue.” At this point, he says, the disease won’t completely go away. But we can address the current out-of-control situation. “It’s a forest fire,” he says. “We need to get it down to something more smoldering.”