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ou’re seeing the signs in pharmacies and perhaps around your workplace. Your doctor’s office may be calling to schedule an appointment. It’s just that time.

Flu vaccination efforts are in full swing.

But you may have been hearing puzzling things about flu shots over the past couple of years.

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While the flu is a common illness, that hardly means the science around it is static. Some recent studies have suggested that getting a yearly shot may actually diminish the benefit of successive vaccinations. Others have raised the possibility that statins —  the commonly used cholesterol-lowering drugs — may actually interfere  with your immune system’s response to influenza vaccine.

Meanwhile, the Centers for Disease Control and Prevention recently recommended against the use of the nasal mist vaccine that many kids prefer over injected vaccine.

So are the shots worth the bother? STAT asked some influenza vaccine experts to break down what we’ve learned lately about flu shots and what you need to know as the winter draws near.

Nasal flu vaccine loses its luster — or does it?

In late June an expert committee that advises the US government on vaccination policy recommended that the nasal spray vaccine FluMist, which has been used by millions, not be used this season.

The reason: Studies conducted by the CDC had shown that for the past three flu seasons the vaccine wasn’t protecting the people who got it.

It’s not clear why. Adding to the confusion, a study by the vaccine’s manufacturer, MedImmune, suggested the mist was effective. (MedImmune is a division of AstraZeneca.)

Both the CDC and the Food and Drug Administration are working with the company to try to figure out what’s going on.

In Canada, meanwhile, kids will have the option of getting FluMist this fall because data gathered there showed the vaccine was working — though not quite as well as injectable vaccine, said Dr. Danuta Skowronski, a flu expert at British Columbia’s Center for Disease Control in Vancouver.

One of the Canadian studies, led by Dr. Mark Loeb at McMaster University in Hamilton, Ont., compared kids vaccinated with the nasal spray vaccine to kids who got flu shots over three flu seasons. He found the nasal spray vaccine worked as the flu shot.

“I think they struck the right balance in that decision,” Skowronski said of the experts who decided to retain the vaccine in Canada.

How can we make sense of all of this conflicting information? There are some theories.

FluMist seemed to work well in the United States until MedImmune changed its formulation a few years ago to put an extra component in the vaccine. It had protected against three flu virus families; now it protects against four. Maybe something happened in that process?

Or perhaps repeatedly vaccinating children with this vaccine is diminishing its effectiveness?

For now, there’s no answer. While the search for one continues, the CDC has recommended US doctors not administer FluMist this flu season.

The vaccine triggers the immune system to create antibodies, preparing the body for viral battle. Alex Hogan/STAT

Questions over the impact of repeat vaccinations

There have been suspicions for decades that getting a flu shot year after year might invoke a law of diminishing returns. Those suspicions stem from a 1970s study in which a researcher observed that boarding school students who were vaccinated each year were more likely to contract influenza.

In the late 1990s a British researcher named Derek Smith hypothesized that repeated vaccination could trigger beneficial results — which he called positive interference — when the viruses the vaccine targets were different from one year to the next.

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But he also suggested when the vaccine targets the same specific virus in successive years, the antibodies created in the first year might dampen antibody production the second year. He called that negative interference.

In recent years, a new method of measuring the effectiveness of the flu vaccine has put this theory back on the table. In 2014 scientists from Marshfield Clinic Research Foundation in Marshfield, Wisc., found that people who received the flu vaccine generated higher levels of antibodies — compared with people who received an annual shot — if they hadn’t been vaccinated in the previous five years.

So, is it a thing?

Dr. John Treanor, an influenza vaccine expert at the University of Rochester in New York, said it appears there’s something there.

“It’s really unclear exactly what the mechanism is and I think that’s going to be an area of very intensive investigation over the next few years,” said Treanor.

The problem is, even if the theory proves true, it would be hard to act on the information, he noted. Flu vaccine contains protection against three or four types of viruses, depending on the brand. It is very rare that all four viruses would change from year to year.

So one year you might not really need a repeat of one component, but you would need the other two or three. Because of the way vaccines are made, it’s impossible to unbundle the components.

Still, understanding what is going on is important, said Skowronski.

“For me anyway, these repeat vaccine effects are among the most important developments in influenza vaccinology of the past decade,” she said, noting the issue could have implications for universal vaccination programs, such as the one in the United States, where it’s recommended that everyone get vaccinated against influenza.

“The long-term implications of that frankly are not known and these repeat vaccine effects may have a huge bearing on that.”

In the meantime, experts stress that while repeat vaccinations could lead the body to generate fewer antibodies, it’s still recommended to get a yearly shot. Some protection is better than none.

The statin factor

Statin use has become ubiquitous among people in late-middle age and older seeking to lower their cholesterol.

But two studies published last fall (here and here) suggest that people on statins don’t mount as vigorous an immune response to flu vaccine as people not taking the drugs. The effect was particularly pronounced for people taking synthetic statins.

Inspired by that work, the researchers at Marshfield did a study of their own. They found statin use seemed to lower antibody production to one family of influenza A viruses (the H3N2s) but not to another (H1N1s) and not to influenza B viruses. In other words, this is another question that needs answering.

Loeb said the issue bears studying, but hasn’t yet been proved. “I think there’s some biological rationale [but] it’s definitely not a slam dunk by any means.”

The $64,000 question

So how good is flu vaccine at protecting against influenza?

In the not-too-distant past, the CDC and other public health institutes estimated that flu shots cut one’s risk of contracting flu by between 70 percent and 90 percent.

But that new way of assessing vaccine effectiveness we talked about earlier has shed more light on that question, and the effectiveness estimate was seen to be too high.

The more common claim is that the vaccine lowers one’s risk by an average of about 50 percent to 60 percent — though some years the protection is far less, depending on how well matched the viral targets in the vaccine are to the viruses making people sick.

Everyone wishes the vaccines were more effective. Research is underway to try to develop a flu shot that would provide broader protection that wouldn’t have to be administered every year.

But the science isn’t there yet. And bringing a brand new type of flu vaccine through licensure and to market would cost boatloads of money. So for now, manufacturers in the crowded flu vaccine market are, as Skowronski put it, “tinkering” — adding the fourth component to the vaccine, creating a high-dose product for seniors, who don’t respond as well to flu vaccine, or adding an adjuvant (a compound meant to amp up antibody production) to another vaccine for seniors.

“You get maybe little marginal benefits here, there. But in terms of a real game-changer … I don’t see it,” Treanor said.

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Yes, there are questions about flu vaccine that need to be explored through scientific study. But in the meantime, Skowronski said, people should stay the course.

“You could become overwhelmed by the smorgasbord of issues that have arisen when we started to really systematically evaluate influenza vaccine performance on an annual basis,” she admitted.

Treanor agreed.

“The recommendation and the message that people should be vaccinated still holds true. Because it’s clear from all these studies that although many factors can influence how well the vaccine works, getting the vaccine is always better than not getting the vaccine,” he said.

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  • The problem of repeat flu shots is worse than this article lets on.
    http://www.cidrap.umn.edu/news-perspective/2013/03/study-getting-flu-shot-2-years-row-may-lower-protection This is 2013 study and flu shot effectiveness can go down to zero.
    http://www.cidrap.umn.edu/news-perspective/2014/11/study-adds-more-data-effects-consecutive-year-flu-shots this is 2014 same problem.
    Also studies now show that taking flu shots every year leave you wide open to getting a serious pandemic flu when the next one comes along. You should only take a flu shot when the pandemic comes.
    http://sciencenordic.com/too-many-taking-flu-vaccine .
    Don’t worry you are not gong to die of the flu in the mean time. Do you know anyone who has died of the flu? I don’t, even my doctor has never seen a flu death. Americans have developed an unreasonable fear of the flu. The CDC says there is 3000 to 49,000 flu deaths a year, but the fact is over the last 20 years there has never been more than 6000 deaths. 85% of flu deaths are over 65, so if your under 65 your chance of dying of the flu is about 2 in a million.

  • Have had flu vaccine on anual basis since 65 and my wife had her first one this year. We are at present suffering from a really bad attack of flu . Not a cold as we are medically trained and know the difference. I am questioning the effectiveness of this vaccination program . The vaccination offering a false sense of security could be doing more harm than good .G

    • Are you serious Gordon? Havent you read the scientific (real reports not those paid for by pharma and CDC) on the damage to your health of flu shots? You get 3 flu shots I think, in 3 years 200% increase in alzeimers. They have a hell of a lot of mercury in them……………. angela coral eisenhauer (fb) and YOUR flu shots USA this year, is fluvax, just google fluvax scandal western australia 2010

    • bollocks…………………………………….. your flu vaccine this year is FLUVAX, many different names, killed or maimed so many in Australia in 2010. There is no flu in Australia, cause we dont vaccinate, after those scandals, Johnny, tell me you are not a paid shill from PR teams Mumbai?

  • Instead of focusing on the flu vaccine with variable efficacy and known health risks, why not focus on improving immune system function? Ultimately, whether one takes a drug to treat an infection or submits to a vaccine to prevent an infection, it is the immune system that brings the person back into homeostasis. So, why not support the immune system? Vitamin D3 supplementation is a very effective and inexpensive way to prevent influenza and the more common influenza-like illnesses that occur in the winter months.

  • Well honestly, I don’t know which vaccines are made in which country. And it probably doesn’t matter as long as they go through the proper approval procedures. I think the TGA handles that.

    I was just pointing out the you seem to be implying that AHan does not know what they are talking about just because they live in another country.

  • I’m curious about flu vaccine & associated cardio-protective effects I heard about a few years ago. I’m wondering what the latest research is uncovering. I’m going to get the vaccine. Even reducing by the low end of 25% is worthwhile, imo.

    • Yeah, I agree, how to spread disease, called CDC and pharma fraud. Dtap now, it working real well (spreading whooping cough). Stats, USA:
      1940s 150 cases per 100,000
      1970s 0.5 cases per 100,000
      And along came Dtap is crap in 1996 (?)
      2012, 230 cases of whooping cough per 100,000 (all in kids younger than 20, so lets say 230 cases per 20,000 Dtap vaccinated kids)
      Also, before the vaccine fails, those kids been spreading whooping cough for 6-12 years.
      Every infected newborn, has been infected by a vaccinated child, usually a symptomless sibling. Strange how CDC havent noticed, eh?

  • 2010 Fluvax, also known under about five other names, killed and maimed more than 1 in 100 babies, and toddlers that had it.
    It has double the mercury of a multi dose vial of flu vaccine.
    Death and destruction, for a fraud vaccine. Flu shots dont work, flu mist got banned because all it does is spread the flu.
    Biggest con in history. Read about the old Spanish flu, supposedly spread by returning soldiers? Look at the graphs, the people all died, BEFORE the soldiers got home, all because USA had all these vaccines, and the war only lasted a year for USA< so they flogged them all off to the public, all vaccine deaths, all of them.

    • Angela– Virtually nothing in your post is true. Just a bunch of tin-foil hat conspiracy theories. Your “statistics” are based on 101 children in Australia becoming ill in 2010. The findings had nothing to do with mercury but were found to be the result of viral traces in the vaccine. Flu mist is not “banned”.

    • AHan is english your first language? Everything I say is totally true, and all referenced on my facebook timeline. I live in Australia mate, I live where this happened. I never said the mercury did it, just pointed out it has double the mercury that a multi dose vial has, not good in a 6 month old baby eh? Well if you said it was viral contamination? Hardly good in kids vaccines. You live in India, so you wouldnt know.

    • Ms. Eisenhauer: We expect civil discourse in STAT’s comments section. More posts like this and we will exclude you from commenting.

    • You did: “flu mist got banned because all it does is spread the flu.”
      For the record, since facts actually DO matter, no it doesn’t spread teh flue. And single-dose and preloaded syringe flu vaccines have NO mercury.

    • Patrick, that is a perfect question from an Australian, we have many different cultures in Australia, not all have English as a first language. It is a common question here, I am sorry if that offends anyone. What you are reading into a simple question, is your bias, not mine. The name is A Han. I am quite good at translating, if need be.

    • Hi Angela. Just some personal observations.

      I live in Australia too. I very rarely hear the question “Is English your first language?”

      When I do hear it, it is usually meant as an insult.

      Just because someone lives in a country doesn’t automatically mean they understand the complexities of specific events in that country.

      Just because someone does not live in a certain country does not mean they can’t understand what happens in other countries. If that were the case, you should probably leave comments about the US CDC and US pharmaceutical companies to those who live in the USA.

    • Most vaccines were first used a long time after 1918……First flu vaccine was produced in 1938, by Dr Salk of Polio vaccine fame.

    • McSpac, all that would be true, if the same vaccines were not sold to Australia. Do you seriously think we dont use USA vaccines?

    • Robert Baden, I never said they were flu vaccines, used in 1918. USA vaccine manufacturers, had lots of vaccines. The first world war ended only a year after USA entered. The vaccines used on the soldiers had made them very ill (they still testing vaccines on soldiers, 45,000 ill now in USA after Afghanistan, and only 150 killed in battle?)………..
      So, they created fear, just like they do now, all the soldiers are sick (which they were from the vaccines)………… so they began vaccinating the population, against this mythical disease, called Spanish Flu. Most of the poeple had died, BEFORE THE TROOPS EVEN CAME HOME. Most died before the end of WW1, the sick soldiers came home to an empty house.
      Pharma murder, cover up, just like now, with the microcephalic vaccine damaged babies, USA and Brazil from the untested vaccines, they now give in pregnancy.

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