Typically, vaccines safeguard you against a single, specific illness. They inform the immune system about what that invader will look like, enabling your cells to be prepared to spring into action.

However, some vaccines do something slightly different.

For example, during the pandemic, researchers noticed that people who received the BCG vaccine against tuberculosis—which is not recommended in the U.S. but is commonly used in countries where the disease is endemic—had additional protection against COVID-19. This aligned with decades of observations that the vaccine prevents a variety of other diseases. Although the vaccine itself has a mixed success rate, the way it functions has intrigued scientists: it turns out that BCG boosts the innate immune system, which is not specific to a particular pathogen, and provides broad, albeit low-level, protection against numerous different infections.

So, is there a way to create a more comprehensive vaccine—one that can protect against multiple viruses and bacteria simultaneously? In Science, researchers describe a vaccine, administered as four doses of nasal spray, that prevented mice from being infected by flu, COVID-19, SARS, and a bacterium that causes respiratory infections. The findings need to be confirmed, and the vaccine approach must be tested in other animals, including humans, before its true significance becomes clear. But the study offers a tantalizing glimpse of a fundamentally different and far-reaching method of preventing disease.

A curious mix of ingredients

The aim was to stimulate immune pathways similar to those triggered by BCG, without including a live bacterium, as that particular vaccine requires, says Bali Pulendran, a professor of microbiology and immunology at Stanford University and an author of the new study. Consequently, the new vaccine contains a combination of substances intended to stimulate several aspects of the immune system.

When the researchers gave the treatment to mice over a four-week period and then exposed them to pathogens, what they observed was promising. “One month after immunization, three months after immunization, and in some cases, up to six months after immunization, the mice were protected against SARS-CoV-2, the original SARS pathogen, and another coronavirus,” as well as other pathogens, says Pulendran. Further exploration revealed that the vaccine had induced the formation of tiny immune structures in the lungs, fortresses from which the mouse’s body could continuously combat infection.

Those structures appear to be crucial, says Akiko Iwasaki, a professor of immunology at Yale School of Medicine who was not involved in the study but describes it as “very interesting.”

“In humans, there are different structures in the nose, throat, and deeper lung,” she says. “Whether this type of vaccination can induce similar structures in humans is something that needs to be tested.”

Further work needed

Indeed, the next step in building on these results will be further testing, says Pulendran. Humans and mice, although they have similarities, are different in many ways that could thwart efforts to bring this approach closer to application. A vaccine that can protect against multiple diseases simultaneously is still a long way off.

But this research is an interesting step in that direction, says Ellen Foxman, a professor of immunology at Yale School of Medicine who was not involved in the study. “It’s a really exciting idea. And in my opinion, this is also a trending idea in immunology,” she says, noting that the effects of BCG during the pandemic have made many researchers think about how to achieve broad protection with new types of vaccines. While this study may be among the first to investigate this relationship, she anticipates seeing more work along these lines in the coming years.

As researchers explore a potential vaccine like this one in humans, they will undoubtedly uncover some surprising details about how immunity functions. “I think there’s a lot of rich new biology here,” says Pulendran, who is curious whether a similar approach might work for diseases beyond respiratory ones.

The process of understanding how the human immune system responds to such a treatment will surely be illuminating, says Foxman. “We’ve had decades of experience with the typical vaccinations we’ve had. There’s decades of knowledge about how they work in humans,” she says. “And for this sort of thing, there’s really no experience yet of how it works in humans. So that’s the open question.”