How the Flu Shot Is Made
The story behind your seasonal vaccine
En español | For most of us, flu season begins each fall. For flu experts in the United States, however, it might as well begin in February.
That's when scientists and researchers from around the world gather for a meeting hosted by the World Health Organization (WHO), where they spend days reviewing which strains of the flu virus have been making people sick and decide which strains the next season's vaccine should cover.
But when experts touched down in Beijing this year, their goal — to recommend a vaccine formula for the Northern Hemisphere's 2019-2020 flu season — hit a roadblock.
A new variety of the flu virus known as H3N2 had begun to spread rapidly in several countries. In the United States, it caused a second wave of illnesses late in a flu season that had already seen the rise and fall of another strain entirely.
"That was something that we were concerned about and wanted to incorporate into the Northern Hemisphere vaccine … so we delayed the H3N2 decision by a month,” says virologist and physician Kanta Subbarao, director of the WHO Collaborating Centre for Influenza in Melbourne, Australia, one of six WHO centers that help track flu worldwide.
The extra month gave experts more time to analyze the newly circulating virus. By March, they had updated their recommendation to include a suitable H3N2 strain for this season's flu shot, which is now available.
More importantly, the delay proved an old truth about an ancient virus: The flu is a moving target, and for the network of laboratories, agencies and manufacturers who help make the flu vaccine each year, tracking it is only the start.
A needle in a haystack
The challenge starts with the virus itself.
An expert shape-shifter, the flu is constantly changing — mutating as it replicates itself — in ways that allow its strains to get past our body's immune defenses even if we've had the flu before, or if we roll up our sleeves for the shot each fall.
The result? “It's a bit of a war between us and the virus,” says David Wentworth, director of the WHO Collaborating Centre for Influenza in the U.S., which is run out of the Centers for Disease Control and Prevention (CDC) in Atlanta.
This battle plays out not only within the bodies of people who come down with the flu's signature fever, chills and muscle aches, but also in laboratories around the world, where researchers must work quickly to analyze how the flu virus is changing in order to predict what it might do next.
The worldwide system of surveillance starts when specimens from sick patients are sent to the lab for testing. Of those, about 7,000 end up at the laboratory run by microbiologist John Barnes, who leads the CDC's influenza genomics team.
"We're always busy, and we're always getting new viruses to work on,” Barnes says. He and his team perform year-round genetic sequencing to determine how flu viruses are behaving, both in terms of which strains are infecting people and other characteristics, like whether a specimen shows signs of resistance to the antiviral drugs that can treat the flu.
From there, about one-third of the CDC specimens will undergo further assessment as part of a labor-intensive process known as antigenic testing.
“Almost every season's a little different, and the viruses that circulate have nuance,” Wentworth says. “We're looking for a needle in a haystack.”
Making the flu shot
The pressure also is on for U.S. manufacturers, who have about six months after that first February meeting to prepare, test and ship more than 100 million doses of the vaccine, which start to show up at doctors’ offices and drugstores across the country by August.
In Swiftwater, Pennsylvania, the process begins with a chicken egg — or rather 1 million of them. They arrive every day during flu shot production season at the plant owned by Sanofi Pasteur, the world's largest manufacturer of flu vaccines.
The fertilized chicken eggs are injected with the viruses that have been selected for that year's vaccine, then left to incubate for several days before the virus is extracted and inactivated for use in the flu shot.
"It may sound like an old-fashioned technology. It isn't,” says physician Monica Mercer, the company's director of scientific and medical affairs. Today, around 95 percent of all flu vaccines made in the United States start out in eggs, even as manufacturers look to new technologies, like growing the virus in cell cultures, as an alternative.
One vaccine innovation that's already widely available: flu shots formulated specifically for older adults, who scientists have long known tend to respond poorly to the vaccine for the same reason they are more susceptible to the flu in the first place — the weakening of the immune system as we age.
Pigs, pandemics and a better vaccine
But even the most effectively formulated seasonal flu shot is, by design, only intended to protect people from the types of flu that commonly circulate in humans.
Among researchers, another main area of concern is the possibility of a flu pandemic, which occurs when a flu virus that typically infects animals, like pigs or birds, changes in such a way that it can spread rapidly — and perhaps lethally — from person to person.
That's where experts like veterinarian and professor Andrew Bowman, who leads Ohio State University's animal influenza research program, come in.
Bowman and his team spend each summer traveling to more than 100 county fairs, where they swab the snouts of exhibition pigs in search of flu strains with pandemic potential. Much like the CDC researchers who analyze human flu specimens, their goal is to use genetic testing to get an early look at potentially troublesome changes in the viruses they capture.
"As we characterize these strains, we can identify viruses that might be able to spread human-to-human so that we can have effective countermeasures in place before ... an outbreak,” Bowman says. These countermeasures include collaborating with the CDC to have the building blocks of a pandemic flu vaccine at the ready, should the need arise.
But it doesn't take a pandemic for the flu to be a serious, even fatal, health threat — especially for older adults.
"The typical patient that gets complications from the flu is usually an older person, and usually somebody with an underlying medical condition,” says emergency physician Jeremy Brown, author of Influenza: The Hundred-Year Hunt to Cure the Deadliest Disease in History.
When to get your flu shot
It takes about two weeks to build up immunity after receiving the flu shot, so experts say early vaccination is key: The CDC recommends getting the flu shot early in the fall, by the end of October.
If you're 65 or older, ask your doctor about the high-dose or adjuvanted version of the vaccine, which is formulated specifically for older adults.
According to the CDC, an estimated 90 percent of flu-related deaths and 50 to 70 percent of all hospitalizations for flu occur among people age 65 and older. While the effectiveness of the flu shot varies from year to year, the agency estimates that it prevents millions of cases of flu and flu-related doctor visits annually.
Still, Brown notes, there is room for improvement. Typically, the flu shot is about 50 percent effective, but that rate has dipped as low as 19 percent in recent years. In those cases, he says, low rates might be the result of a vaccine formula that isn't well matched to the viruses that end up going around, despite the experts’ best prediction. They might also be caused by a vaccine that, although well matched, just doesn't stimulate our immune systems like it should.
One hope, he says, is that a universal flu vaccine that protects against all possible strains of the virus could someday replace the yearly shot entirely. But despite early trials, he says the prospect is still a long way off.
In the meantime, the flu virus continues to change, evolving in ways both expected and unforeseen. The expert advice, on the other hand, remains the same: Get the flu shot. Your future self might thank you.