Getting a flu shot every year? More may not be better

If you’ve been diligent about getting your flu shot every year, you may not want to read this. But a growing body of evidence indicates that more may not always be better.

The evidence, which is confounding some researchers, suggests that getting flu shots repeatedly can gradually reduce the effectiveness of the vaccines under some circumstances.

That finding is worrying public health officials in the US, who have been urging everyone to get a flu shot each year — and who still believe an annual vaccination is better than skipping the vaccines altogether.

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Dr. Edward Belongia is among the scientists who have seen the picture coming into focus. He and some colleagues at Wisconsin’s Marshfield Clinic Research Foundation reported recently that children who had been vaccinated annually over a number of years were more likely to contract the flu than kids who were only vaccinated in the season in which they were studied.

“The vaccine was significantly more effective … if they had not been vaccinated in the previous five years,” Belongia, an epidemiologist, recounted in a recent interview with STAT.

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Vaccines work by exposing the immune system to a part of a disease agent — in the case of influenza, to two proteins on the exterior of the viruses — that has been rendered harmless. The vaccines tell the immune system to be ready to mount an offensive if it encounters the specified invaders.

The immune system then produces stores of protective ammunition — antibodies — it can use to fight off infection.

With many vaccines, an additional dose or two boosts the levels of antibodies in a person’s body. Some vaccines actually require multiple doses to be effective.

So the fact that repeated vaccination against flu might diminish rather than enhance the vaccine’s protection is perplexing.

It also represents a communications challenge for public health officials who vigorously promote annual vaccination as the most effective way to protect against the flu. Findings that suggest the science is more complicated than initially believed could lead people to assume annual flu shots are detrimental to their health.

That’s not the message researchers such as Belongia want to convey.

“In every scenario, it is better for people to be vaccinated than not vaccinated,” he said. “It would not be, I think, accurate or helpful for people to take away from this ‘Oh, well, I shouldn’t get vaccinated because I got vaccinated in the past and that’s a bad thing.’ ”

Like most issues related to mysterious and mercurial flu viruses, this one is a complex puzzle. But several researchers say the effect appears to be real — and needs to be explored further.

A number of countries are trying to get ever-larger portions of their populations immunized annually against influenza, a fact that makes it all the more important to figure out what is going on, flu experts say.

“The influenza immunization program is our largest, most costly annually repeated immunization program,” said Dr. Danuta Skowronski, an epidemiologist at the British Columbia Centre for Disease Control in Vancouver. “It’s worth it — so worth it — to invest in understanding these effects.”

But getting answers means mounting prospective, randomized clinical trials, and that will be both expensive and complicated.

The work cannot be done in the United States, where the Centers for Disease Control and Prevention has recommended since 2010 that everyone receive annual flu vaccinations. Given that policy, it would be unethical for researchers here to randomly assign some people to forgo vaccinations in some years. But experts elsewhere, including in Hong Kong, where influenza circulates year-round, are trying to put together the funding for what would have to be a large, multiyear study.

The question of the effectiveness of repeated flu vaccines has actually been kicking around for decades. Back in the 1970s a researcher noticed that children at a boarding school who were vaccinated year after year seemed more likely to catch the flu. Later studies disputed the suggestion.

Like most issues related to mysterious and mercurial flu viruses, this one is a complex puzzle.

Then in 1999, a leading influenza researcher, Derek Smith, suggested that in years when a component of the vaccine — say the part that protects against the influenza A family called H3N2 — had changed little or not at all from the previous year’s vaccine, the second year’s vaccine would induce less protection. Smith, now based at Britain’s University of Cambridge, called it negative interference.

The idea is that the antibodies produced in year one may neutralize some of the vaccine in year two’s shot before it can trigger a full immune response, explained Dr. John Treanor, a vaccine expert at the University of Rochester Medical Center in New York.

Smith also argued that when the vaccine viruses were quite different from one year to the next the recipient would actually get enhanced protection. Positive interference, he called it.

Skowronski started to see evidence of negative interference in the mid-2000s, when she and a fellow Canadian researcher, Dr. Gaston De Serres of Quebec’s public health agency, found the flu vaccine was significantly less effective than they had expected. Conventional wisdom at the time was that it cut the risk of catching the flu by 70 percent to 90 percent. But even during flu seasons when the vaccine was well-matched to the viruses making people sick, it wasn’t proving that effective.

In their search for answers, the researchers considered the people they were studying. About 90 percent were getting flu shots every year. “They’re habitual immunizers,” Skowronski said.

Figuring out whether negative interference is real and what can be done about it is important, Treanor said. But if the phenomenon really exists, researchers have unearthed a problem without an immediate solution.

That’s because influenza vaccine protects against three or four different families of flu viruses. The vaccines only come in the combination form.

A number of research teams are working to develop a universal flu vaccine, one that trains the body’s immune system to fight off all flu viruses. The goal is to have a vaccine people might need to take only a few times in their lives, maybe once a decade. That might solve the problem, Treanor said — but he noted a universal flu vaccine could be years away.

In the meantime, high-dose vaccines might help ensure that vaccines don’t become less effective over time. The extra vaccine in the shot might override the dampening effect of previous years’ antibodies. But Treanor cautioned that theory hasn’t yet been put to the test. And the sole high-dose flu vaccine available in the US — made by Sanofi Pasteur — is licensed for use only in adults 65 and older.

Likewise, an adjuvanted vaccine — one that includes a compound that boosts the immune response the vaccine generates — might prove effective. Although none is currently licensed in the United States, one may be coming.

As for changing the frequency with which the flu vaccine is given, it’s far too soon to even contemplate that kind of move, Belongia said.

“The policy of vaccinating every year has been generally successful,” Belongia said. “We wouldn’t want to change that unless we know for sure that we’re changing it to something that’s going to be better. And right now I don’t think we have any good idea what that would be.’’