Could a universal coronavirus vaccine be the silver bullet that ends this pandemic—and the next?

Could a so-called “pan-coronavirus” vaccine be the long-awaited silver bullet that ends the COVID pandemic—and the next one, too?

Answer: It’s complicated.

“The term pan-coronavirus vaccine needs an asterisk next to it,” Dr. Stuart Ray, vice chair of medicine for data integrity and analytics at Johns Hopkins’ Department of Medicine, told Fortune.

Such a vaccine could tackle all coronaviruses, named for their crown-like appearance under a microscope. Or it could focus on COVID-19 and its myriad variants. Or it could tackle the four longstanding coronaviruses that circulate as common colds—or any combination thereof.

It could also protect against SARS (Severe Acute Respiratory Syndrome), a coronavirus that emerged in 2002 and killed hundreds, and MERS (Middle Eastern respiratory syndrome), another coronavirus that emerged in 2012 and killed hundreds.

Aside from the possibility of concluding the current coronavirus pandemic, it might even be able to squash the next as soon as it starts.

“Coronaviruses jump over to the human population,” said Dr. Duane Wesemann, a professor at Harvard Medical School and a principal investigator in the Division of Rheumatology, Immunology, and Allergy at Brigham and Women’s Hospital. He’s leading a team of researchers working on a pan-coronavirus vaccine with funding from the U.S. National Institutes of Health.

“I don’t know when [the next will]. Maybe not in our lifetime. But it will probably happen sometime. Is there a way to develop a vaccine that will be available for us in the setting of SARS-CoV-3?”

Whatever form such a vaccine might take, it’s a worthy goal, Dr. Bruce Walker—director of the Ragon Institute of MGH, MIT, and Harvard, a medical institute focused on eradicating disease, and co-leader of the Massachusetts Consortium on Pathogen Readiness—told Fortune.

But it may forever remain just that: a goal.

“I think we have to be aspirational in terms of aiming to make a pan-coronavirus vaccine, but it will not be an easy task,” Walker cautioned. “There’s not an obvious path forward.”

Work underway—and potentially years of work ahead

However pie-in-the-sky the goal may be, there’s no shortage of work being done to accomplish it. A universal coronavirus vaccine is a top research priority for nonprofits, government agencies, and vaccine-makers, according to an April article in Nature.

Among entities with a version in development: Moderna, Duke University, and myriad biotech companies.

Clinical trials are underway for attempts by the U.S. Army and CalTech, Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security, told Fortune.

Such a vaccine could indeed serve as a “silver bullet,” he said: “That would be the way you take this threat off the table—not just SARS-CoV-2, but all coronaviruses. And to knock off 30% of common colds would be a really good thing.”

But these things take time, he said. An apt illustration: the flu vaccine.

“We don’t yet have a universal flu vaccine though people have been working on that for some time,” he said. “There are some versions of a universal flu vaccine in clinical testing, but it’s not something that’s been deemed to have efficacy and hold up over multiple influenza seasons with multiple strains.”

Yet another: HIV.

“We’ve been working on vaccines for some pathogens like HIV for decades,” Wesemann said. “Some scientists several decades ago were thinking, ‘Gosh, it’s only going to be a few years until we have an HIV vaccination,’ but many decades later, we’re still figuring out we have more to learn about how to do this.”

Wesemann said he’s more optimistic about the development of a pan-coronavirus vaccine, “but we learned a lot of humility from other pathogens.”

“We don’t understand our immune system as much as we need to, to sit down and design the best vaccine,” he said.

Making a universal coronavirus vaccine available to the general public will require additional research, animal studies, and early-phase human studies, all of which can take years, Dr. Dan Barouch—a professor of medicine at Harvard Medical School and the director of the Center for Virology and Vaccine Research—told Fortune.

And the process is not occurring on the accelerated Operation Warp Speed timeline the original COVID vaccines were on, Adalja noted.

“It will likely still be a while before a pan-coronavirus vaccine will be available to the general public,” Barouch said. “I don’t think anyone will be going this fall to get this at CVS.”

Promising, but not impervious

Even when—or if—a universal coronavirus vaccine is available, it likely won’t be bulletproof, experts caution.

While a pan-coronavirus vaccine has the potential to “help end the pandemic”—at least in the way of halting severe disease and death—its success would hinge on enough individuals around the world to get the jab, said Dr. Daniel Kuritzkes, chief of the Division of Infectious Diseases at Brighman and Women’s Hospital and professor of medicine at Harvard Medical School.

Otherwise, the virus could learn to evade even a universal COVID vaccine.

“That’s certainly a possibility,” Kuritzkes said.

“So long as the virus continues to circulate in a significant number of people, there’s an opportunity for continued adaptations of the virus,” he added. “Were there to be a variant that emerged that had acquired mutations that were able to evade immune response from the supposed pan-coronavirus vaccine, the virus could leap into the vaccinated population and emerge again.”

There are two goals vaccines can aspire to, Ray said: to prevent infection altogether, or to merely prevent severe disease and disruption, as current COVID vaccines do.

A pan-coronavirus vaccine might prevent severe disease and disruption from all variants and subvariants of COVID-19, theoretically eliminating the need for boosters. 

But such a vaccine may still allow the spread of infection, as current vaccines do, experts warn.

“My guess is if we design a vaccine that’s meant to be as broad as possible, we’re going to have to give up some potency,” Wesemann said.

The pan-coronavirus vaccine concept may simply be too good to ever become reality, Ray cautioned—but he holds out hope that such a development could “hit that sweet spot of really being protective and durable.”

“One of the things that keeps us awake at night is if we do things that don’t control the spread, that it will continue to evolve and find a gap in our armor,” he said.

One possible gap: long COVID, a potentially disabling condition federal officials say could affect up to 23 million Americans who’ve survived infection.

Research shows that “even mild to moderate COVID can have long-term consequences for cardiovascular and mental health outcomes,” Ray said. “We might find we prevent the severe first couple of weeks of disease but see an accumulation of damage from relatively mild infections.”