This Is How Scientists Decide What Goes In Your Flu Shot

Developing the flu vaccine is a bit like predicting the weather. Experts must track influenza patterns around the world, plug data into models, and make educated guesses about what to expect during flu season. And they must update their forecasts each year.

“Influenza is one of the few viruses for which the vaccine is updated on an annual basis,” says Andrew Pekosz, director of the Center for Emerging Viruses and Infectious Diseases at Johns Hopkins University. “It’s because the virus mutates and changes so much during the course of one or two flu seasons that we constantly have to be updating the vaccines.”

All year long, researchers like Pekosz collect data on the flu viruses circulating in more than 100 countries. They monitor which strains of the virus are causing infections, how efficiently those strains are spreading, and how well previous vaccines have worked to combat those viruses.

There are hundreds of strains of influenza, but they can all be divided into two main classes: variants of influenza A virus, and variants of influenza B. The proteins on the surface of each strain look unique to the human immune system. And each year, they evolve just enough that immune cells no longer recognize these proteins, so you’re no longer protected against influenza.

That’s where the flu shot comes in, Pekosz says. It helps teach the immune system to create antibodies that’ll fight off common strains of influenza when you’re exposed to them.

Scientists and public health officials at the World Health Organization and the US Centers for Disease Control make recommendations for the composition of the flu shot by pooling their data on the viruses together each year. They narrow down the top candidates for the vaccine to the three or four influenza strains most likely to make people sick. These top strains are announced in February or March, about nine months before flu season. It then takes companies some time to manufacture the flu shot.

Most manufacturers grow flu viruses in fertilized chicken eggs. Once scientists have isolated the influenza strains they need in the lab, they inject the viruses into the allantoic fluid between the embryo and the shell. The viruses replicate really well in this environment, and can be harvested a few days later. The resulting fluid is then purified, the viruses are weakened or killed, and just the virus surface protein—or antigen—ends up in the flu shot.

Since 2013, a few flu vaccines have been created using recombinant technology. Antigens for these vaccines are taken directly from the flu virus and combined with DNA from another virus. The combo is grown in a culture of armyworm cells in the lab, before being harvested and purified. This helps speed up vaccine production and may also avoid mutations that scientists have found introduced in vaccines as influenza viruses adapt to growing in chicken eggs.

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Ultimately, immunologists hope to create a universal flu vaccine—one shot to provide lifelong protection against all virus strains. It’s no easy task, but researchers are concentrating on finding portions of the influenza virus that mutate less rapidly than the surface hemagglutinin proteins. Targeting the “stalk” of the proteins deep inside the virus has shown some success in protecting mice in recent experiments. But it’s still far from ready for human use, says Pedro Piedra, a pediatric infectious disease specialist at Baylor College of Medicine in Houston, Texas.

Until then, everyone six months of age and older should get the flu vaccine every season, Piedra says. “If we can have a vaccine coverage level of 90 percent, then we’ll have much greater impact against the flu, even if the vaccine is not perfect,” he says. “And we can do a lot to improve the current vaccine coverage in the United States.”

Healthy adults often underestimate the flu, so less than half get vaccinated. And chances are if you get it, you’ll have a cough, runny nose, fever, and generally feel crummy for about a week, Piedra says. But the symptoms are usually more severe than a common cold, and they can result in lost wages, medications, and hospital bills. Each year, 5 percent to 20 percent of the US population ends up getting the flu, tens of thousands are hospitalized, and around 12,000 people die from flu-related illness, according to CDC estimates.

Once a flu outbreak begins, scientists and doctors can’t do much to stop it. Experts simply continue tracking the severity of the flu season and update their information on the circulating strains, vaccine efficacy, and number of people affected in order to better predict the next year, Piedra says.

Sometimes the flu shot turns out to less efficacious than expected. That may happen when scientists get the composition of top viruses for the vaccine wrong, or when one of the viruses mutates in the months of manufacturing and testing. “That doesn’t mean that the other components of the vaccine didn’t work,” Piedra says. “And that doesn’t mean that [less effective] component didn’t work in a particular individual. But in general, at a population level, the vaccine may not have been well-matched to the major circulating virus.”

Better forecasting models will help experts predict flu seasons more accurately and earlier than in the past. One such model being tested at the University of Chicago accounts for both changes in the virus strains and how the virus spreads. It may allow health officials to manage their resources and make outreach efforts to increase vaccine coverage in the most susceptible groups.

Right now is a good time to get the flu shot, says Gregory Poland, head of the Mayo Clinic's Vaccine Research Group in Rochester, Minnesota. “One of the things that people often think is that ‘Oh, if I didn’t get it by Thanksgiving or Christmas, it’s too late.’ But that’s not true,” he says. “Our largest influenza outbreak in the US on average is in February.”

After getting the flu shot, it takes two or three weeks for the body to develop immunity against influenza. Then you’re protected for the rest of the flu season, although Poland still recommends taking extra precautions like washing your hands properly, sneezing into crook of your arm, and staying at home if you feel an oncoming case of the sniffles.

“The influenza vaccine is like a seatbelt,” he says. “Is it perfect? No. Is it better than not having it? Absolutely.”

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