What if you could be vaccinated against all types of the flu forever?

Researchers are stepping up the search for a vaccine that would provide immunity to all strains of the influenza virus. Current vaccines only target the parts of a virus that vary from strain to strain, and must be updated every year.

The current vaccines are effective, reducing the number of hospitalizations as a result of flu infections each year. But they don’t guarantee that a vaccinated person won’t get the flu. That has made flu vaccines a tough sell for public health officials. Roughly 60 percent of people in the United States are expected to get a flu shot this year.

Read More: Health Concerns Rise As Swine Flu Sweeps Across India »

So Why No Universal Vaccine?

Research funded by the National Institutes of Health, published today in the journal Science Translational Medicine, explains why researchers haven’t yet been able to develop a broad-spectrum vaccine that would throttle most strains of influenza.

The parts of a given flu strain’s viral structure that it shares with nearly all other strains lie on the stalk of the virus. A universal vaccine would have to stimulate an immune system attack on that area. But these targets, or epitopes, are especially good at avoiding an attack. They’re hard to reach and are only susceptible to a rare type of antibody, according to the paper. The immune system also weeds out the cells that make those antibodies because they tend to attack a wider range of perceived threats, making them more likely to accidentally attack healthy tissues.

“There’s the head approach and the stem approach, and both have advantages,” said Ted M. Ross, Ph.D., an infectious disease expert at the University of Georgia who is researching better “head” vaccines.

But scientists aren’t ready to throw in the towel on a vaccine targeting the stalk.

“What we’re trying to explain is how to overcome this. You need to know why these epitopes aren’t targeted first in order to design vaccines that will target them,” said study author Patrick Wilson, Ph.D., an associate professor in the department of medicine at the University of Chicago.

Read More: One Mutation Allowed Flu Virus to Become Resistant to Last Year’s Vaccine »

Learning From a Pandemic

Efforts to boost immunity to targets on the stalk of the flu virus gained urgency after the 2009 H1N1 “swine flu” pandemic.

The 2009 strain was very different from those that had come before. To attack it, human immune systems dug deep to find a bit of the virus that they’d seen before. They unleashed antibodies that went after those familiar targets on the virus’ stalk.

The response, though unusual, seemed to be quite effective: The new strain was nearly eradicated. It’s not clear that the specifics of the human immune response can take credit for its destruction, but the event certainly got researchers’ attention.

The question now is, can we trigger equally effective responses with a vaccine?

Perhaps. But the new study shows that the body attacks broad targets only the first time it sees a new virus. After that, it goes back to a narrower defense.

That means that a person who has been exposed to more variants of the flu virus — including the bits of inactive virus that come in a flu shot — is less likely to mount a broad attack on the latest strain of virus.

That’s the study’s most startling finding. The more an individual has had the flu, the less effective a broad-spectrum vaccine may be.

“So even if we came up with a good stalk vaccine it may not work in humans,” Ross said. “It’s different if you talk about children, who don’t have a lot of immune memory, if you started them off with stalk antibodies.”

But because a universal vaccine would bring enormous benefits, scientists want to keep trying to overcoming the hurdles laid out in the new paper.

“I think that a designed vaccine that would target these epitomes in a dominant way could overcome these issues,” Wilson said.

Early work developing vaccines that would target a broader spectrum of viruses is already under way.

“That’s kind of where we’re at, “Wilson said. “They’re doing what needs to be done.”