For the past eight years, flu shots around the world have contained a virus that was retrieved from a sick person in California in the spring of 2009, in the earliest days of the H1N1 — or swine flu — pandemic.
Recently, the World Health Organization recommended that flu vaccine manufacturers swap out the component that is based on that virus with an updated version. It is uncommon for a flu virus to remain in the vaccine for such an extended period as the current one.
"A/California had a good run," Dr. Danuta Skowronski, an influenza epidemiologist at the British Columbia Center for Disease Control in Vancouver, said of the virus that is being discarded.
The change, which will first come into effect in the flu shots for the 2017 Southern Hemisphere winter, is good news. It's an indication that advances in flu science — particularly relating to monitoring small changes in viruses and figuring out how that evolution dictates who and how many people might get sick in a flu season — may be helping scientists fine-tune flu-fighting strategy.
Flu vaccines work by exposing the immune system to proteins on the exterior of influenza viruses that have 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.
The latest change was made, experts say, because it had become apparent that a portion of people — some people between the ages of about 30 and late middle-age — were not getting as much protection from the part of the flu shot that is supposed to guard against infection with a family of influenza A viruses called H1N1.
Normally, healthy adults generate the best response to vaccines. But in the past couple of seasons, that hasn't been the case for the H1N1 component. Paradoxically, though, children and older adults were still developing good levels of antibodies to H1N1 after getting vaccinated.
The virus being replaced is called — wait for it — A/California/7/2009 (H1N1)pdm09-like virus. The lay translation: It is an influenza A virus of the H1N1 family that emerged in the 2009 pandemic. It was recovered in California that spring, when the first illnesses linked to the new virus were spotted.
On the advice of flu experts from around the globe who met in Geneva recently, the WHO is recommending the virus be changed to a virus from the same family retrieved from a patient in Michigan in 2015.
The change should mean better protection for the segment of the population that wasn't getting as much benefit from the California virus, without diminishing the protection the vaccine offers children and the elderly, said Jacqueline Katz, deputy director of the influenza division at the Centers for Disease Control and Prevention in Atlanta.
Katz is a member of the WHO's influenza strain selection committee, which meets twice a year to analyze which flu viruses are circulating around the globe and recommend which should be targeted by the Southern and Northern hemisphere vaccines.
One of the things that is interesting here is that a change is being made to try to fix a problem facing only a portion of the people who get flu vaccine. Typically decisions about strains that should go into flu vaccine are made from one-size-fits-all point of view.
"We don't make age-based vaccine strain decisions. So if the vaccine isn't protecting well the non-elderly adults, but seems to function OK in the young, what do you do with that information?" Skowronski said last week, discussing the challenge the WHO's strain selection committee would face.
The science that led up to the decision is also noteworthy. Scientists are now able to monitor the effectiveness of the vaccine in closer detail than in the past, and to see how it performs in different age groups and by virus.
For several years after the 2009 pandemic, the H1N1 component of the vaccine performed strongly. But in 2013, some of the people studying the vaccine's effectiveness started to notice the H1N1 part of the vaccine was still working well in the young and the old, but not as well in other adults. What was going on?
When laboratories like those at the CDC look to see if changes in flu viruses will help them evade vaccine protection, they generally do the work in ferrets, the time-honored stand-in for humans in flu research.
Naive ferrets — animals never before exposed to flu — are vaccinated against a strain like H1N1. Then their blood is exposed to a new version of that virus. If antibodies in the blood surge to quell the virus, the vaccine still works. If they don't, it's time to update the virus in the vaccine.
In this case though, the ferret experiments didn't show a diminished antibody response. It was only when labs started doing the test on blood samples from vaccinated people — and blood from people of different ages — that the problem started coming into focus.
"If you do that same experiment and instead of using ferret antibodies if you use antibodies from humans that actually received the 2009 vaccine, what you find is that there's a significant number of [vaccinated] middle-aged people that … fail to react to the strain that's actually circulating," said Scott Hensley, an associate professor of microbiology at the University of Pennsylvania.
Work that Hensley and his colleagues have been doing may explain what's going on here.
People in early adulthood and middle age were born in the 1960s, 1970s, and 1980s. And for some of them, the first H1N1 virus their immune systems saw was a virus that emerged in 1977 and circulated until about 1985, Hensley said.
It was a distant relative of the current H1N1 viruses, from a branch of the family that disappeared when the pandemic H1N1, which had been a swine influenza virus, started spreading among people in 2009. Despite the shared name, the viruses were pretty different — so much so that many immune systems didn't recognize the new version.
But a small part of the virus looked a lot like the corresponding section of H1N1 viruses that circulated from about 1977 to about 1985, Hensley said.
The immune systems of people whose first H1N1 exposure was during that period likely recognized the new H1N1, which acted like a booster shot, increasing their antibodies to H1N1 viruses.
That early advantage disappeared, though, in 2013, when H1N1 viruses evolved a bit and lost that segment, Hensley said. Suddenly, people who had this immunological profile didn't have the right type of antibodies to fight H1N1 viruses anymore.
Updating the H1N1 component in the vaccine should solve their problem, said Hensley, who stressed the WHO should be applauded for recognizing the dilemma and making the change.
While this should help Southern Hemisphere residents during their next flu season, what about those of us in the Northern Hemisphere who are currently getting flu shots in advance of the coming winter? The vaccine here doesn't include the update. Does that mean we will face a higher risk of contracting the flu this winter?
In theory, perhaps. But last winter H1N1 viruses were dominant, causing most of the flu cases that occurred. That could mean this family will lay low this season.
"We had such a big H1N1 season last year I doubt we'll have a very robust season this year," the CDC's Katz said.
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