How Close are We to a Universal Vaccine for Respiratory Illnesses?

Vaccines usually protect you against a single, specific illness. They give the immune system a heads-up about what that invader will look like, so your cells are ready to leap into action. 

Some, though, do something a little different. 

For instance, researchers noticed during the pandemic 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 extra protection against COVID-19. That meshed with decades of observations that the shot prevents a smattering of other diseases. While the vaccine itself has a mixed success rate, the way it works has piqued scientists’ interest: BCG revs up the innate immune system, it turns out, which is not specific to a given pathogen, and provides broad, albeit low-level, protection against many different infections.

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So, could there be a way to make a more comprehensive vaccine—one that protects against many viruses and bacteria at once? In a new paper in Science, researchers describe a vaccine, given in 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 will need to be confirmed and the vaccine approach tested in other animals, including humans, before its true significance is clear. But the study provides a tantalizing glimpse of a fundamentally different, far-reaching way of preventing disease.

A curious mix of ingredients

The goal 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. Accordingly, the new vaccine contains a cocktail of substances intended to stimulate several aspects of the immune system.

When the researchers gave the treatment to mice over the course of four weeks and then exposed them to pathogens, what they saw 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. Exploring further, they discovered that the vaccine had induced the formation of tiny immune structures in the lungs, fortresses from which the mouse’s body could continually fight infection.

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

“In humans, there are different structures in the nose and the throat and the deeper lung,” she says. “Whether or not this type of vaccination can induce similar structures in humans is something that needs to be tested.”

Further work needed

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

But this research is an interesting move 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 view, this is also a trending idea in immunology,” she says, noting that the effects of BCG during the pandemic got many researchers thinking about how to produce broad protection with new types of vaccines. While this study may be among the first to probe this relationship, she expects to see more work along these lines in 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 feel there’s lots 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 certainly be illuminating, says Foxman. “The typical vaccinations we’ve had for decades. There’s decades of experience of 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.”