The first data on how well the flu vaccine is working this season in North America has just been published — and it helps explain why everyone appears to be sick right now.
The study, from the journal Eurosurveillance, found that the flu vaccine was only 10 percent effective against H3N2 (the main flu subtype going around in the US this season) among adults aged 20 to 64 years old in Canada — the age group that made up the majority of participants in the study. The protection rate rose to 17 percent when considering all age groups.
In most adults, the study suggests the shot would only prevent 10 percent of H3N2 flu cases. So if 100 in 1,000 unvaccinated people develop flu, the number would drop to 90 in 1,000 among vaccinated people — a very small difference in flu risk between vaccinated and unvaccinated individuals. And more than 80 percent of confirmed US flu cases have involved H3N2.
“The evidence is mounting, from Australia and now from Canada, that the vaccine protection is low [this year],” said lead study author Danuta Skowronski, an influenza epidemiologist at the British Columbia Center for Disease Control. “Given the same H3N2 subtype [is circulating in the US], our estimate of low vaccine protection should also apply to the US.”
For the study, Skowronski and her co-authors compared the vaccine coverage rates in Canadians who went to the doctor and tested positive for the flu with the rates of those who tested negative. In a good year, the flu shot’s effectiveness hovers between 50 and 70 percent. But in years when the H3N2 type of flu virus circulates — as it is this year — the vaccine tends to be less protective.
So Skowronski wasn’t surprised by the dismal data. Plus, in Australia, where the flu season peaks in August and H3N2 struck as well, early estimates suggested the shot was only 10 percent effective there too.
“Our findings reinforce the concerns that were expressed from Australia using the same vaccine [formulation] for their 2017 epidemic,” she said. Flu vaccine effectiveness can vary by country, and the US data has yet to be published, but the Canadian study is telling.
But to understand why the shot appears to be underperforming this year, you need to understand how the flu vaccine is made — a production process that involves eggs.
Whenever H3N2 is the dominant flu strain, vaccines don’t work as well
There are four species of influenza viruses — A, B, C, and D — and seasonal flu is caused by influenza A and B. Every year, different strains of these viruses circulate.
To formulate the flu vaccine, public health agencies essentially make early educated guesses on which strains will make the rounds. And that’s not easy.
In February, long before flu season begins in the US, the World Health Organization offers a prediction, based on surveillance and laboratory and clinical studies. Then each country uses that prediction to approve vaccines in its jurisdiction. (In the US, the Food and Drug Administration makes the final call.)
The potential for error here can dramatically alter the effectiveness of the flu shot in a given season. If vaccine makers prepare for one combination of viruses and different ones end up circulating widely, the vaccine won’t work that well.
But there’s another thing that researchers have recently come to realize also alters the vaccine’s effectiveness: Whenever H3N2, a strain of the influenza A virus, is the dominant flu type in circulation, the vaccine doesn’t perform as well.
Edward Belongia, a senior epidemiologist at the Marshfield Clinic Research Institute in Wisconsin who has studied flu vaccine effectiveness, found that the combined vaccine effectiveness during H3N2 seasons was 33 percent. The flu shot’s effectiveness rose to 54 percent during influenza type B seasons, and 67 percent during H1N1 seasons.
Part of the reason has to do with … eggs
There are a couple of reasons why it’s harder to vaccinate against H3N2. For one, the virus mutates as it moves through the population at a faster rate than other flu viruses — making it even harder to design a shot that matches the circulating virus.
One other reason the flu vaccine tends to underperform in H3N2 years has to do with … eggs. To produce the vaccines, manufacturers need to grow a lot of flu virus — and they discovered long ago that flu virus grows extremely effectively in eggs. So viruses are injected into fertilized hen’s eggs, incubated for several days while they replicate, then harvested from the eggs, killed (or inactivated), and purified to go into vaccines.
“It’s an antiquated process, but it’s time-honored,” Anthony Fauci, the head of the NIH’s infectious diseases division, explained. While flu vaccines developed with more modern (cell-based and recombinant) methods of production have been licensed in the US, it’s not yet clear they are more protective against flu than the egg-based vaccines.
Plus, no other cell system comes close to growing the flu virus as cheaply or efficiently as eggs, and the industry has invested a lot in the egg-production infrastructure. So, Fauci explained, “We are stuck in the [egg-based] way, and it’s tough to transition to a more modern technology.”
But lately, researchers have found that there are problems with the egg-based approach that specifically relate to H3N2.
“In the process of adapting virus to grow in eggs, that seems to introduce further changes to the [H3N2] virus, which may impair the effectiveness of the vaccine,” Belongia said. In other words, while growing the flu virus for vaccines, H3N2 mutates to adapt to the eggs, which seems to result in a vaccine mismatch.
Skowronski, whose research helped uncover the egg problem, thinks scientists will discover other reasons the flu vaccine sometimes underperforms. “I don’t think [egg-based production methods] tell the whole story,” she said, noting how complicated flu viruses — and our responses to them — are.
But eggs certainly tell an underappreciated part of the story. And while scientists pursue the holy grail of a universal flu vaccine, they should also try to understand how our current production methods hamper the vaccines we have now.
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