From the WebMD Archives

Sept. 2, 2020 -- Every year since 2010, the CDC has urged almost all Americans over 6 months old to get a flu shot. And every year we fall far short -- just half of us got vaccinated during the 2018-19 season. One reason: Some people believe the shot just doesn’t work.

Because flu viruses mutate constantly and the vaccine wears off over time, you can’t get vaccinated once and expect to be covered for years, as you can with other diseases. The vaccine must be changed each year, in hopes of matching the ever-mutating viruses. And that’s been a challenge. On average, it’s been 40% effective, meaning it’s prevented illness 40% of the time. Since health officials started tracking it in 2003, effectiveness has varied from year to year, ranging from a low of 10% in 2004-05 to a high of 60% in 2010-11.

Here’s what makes it so difficult. There’s no single flu virus. It comes in several strains, the two most common being A and B. The A strain, the more dangerous of the two, has two subtypes that spread regularly among humans: A(H1N1) and A(H3N2). And the B strain, which tends to cause a milder illness, gets classified into two lines. From there, each one branches out further as new mutations occur.

“When we talk about building an influenza vaccine, we’re not just trying to make a vaccine for one virus, like with the measles,” says Michael L. Jackson, PhD, the principal investigator for the United States Influenza Vaccine Effectiveness Network from Kaiser Permanente Washington Health Research Institute. “We’re trying to make a vaccine for four different viruses all at once.”

Vaccines for A and B viruses were first given in the 1940s. In 1947, investigators realized that mutations in the viruses had made the vaccine ineffective, setting in motion the annual system we have now. Five years after that, the World Health Organization (WHO) established the Global Influenza Surveillance and Response System, which monitors the changes in the predominant flu viruses circulating each year.

Today, more than 100 countries gather information about the flu year-round. The WHO collates that information and spearheads the effort to predict which flu viruses will dominate in the coming year. Each new vaccine includes one A(H1N1), one A(H3N2), and one or two B viruses. For the Northern Hemisphere, those predictions take place in February -- that’s right, while the current flu season is still in full swing, scientists must determine what should be in the vaccine for the next season.

That’s because making the vaccine takes time -- drugmakers need at least 6 months to produce enough doses. Flu viruses mutate quickly, and sometimes by the time the vaccine is ready, a circulating virus has changed, says Jeffrey Shaman, PhD, a professor at the Columbia University Mailman School of Public Health who leads the development of the school’s flu forecasting system. “So what actually comes out in the vaccine is not quite what they intended,” he says.

Another problem: Since they’re working so far ahead, sometimes the virus predictions simply miss the mark. “The majority of the time we get it right, but from time to time we get it wrong,” says Jackson.

How We Track Effectiveness

The U.S. Flu Vaccine Effectiveness Networks began collecting data during the 2003-2004 flu season. Before then, how well the vaccine worked wasn’t routinely monitored. The networks include three groups of hospitals and universities, each focused on a different part of the vaccine’s effectiveness.

At the University of Michigan School of Public Health, Joshua Petrie, PhD, is part of a team that works with the CDC’s U.S. Flu Vaccine Effectiveness Networks. The program recruits patients from outpatient clinics who come in because of a respiratory illness that might be related to the flu. Tests determine whether or not each patient has the flu, and researchers like Petrie compare the proportion that are vaccinated in those who tested positive to those who tested negative. “If the vaccine works well, we expect a higher proportion of negative people to be vaccinated,” he says.

The data gathered by the various networks gets adjusted to account for differences in age, race, and medical conditions, then researchers determine the estimated effectiveness each year.

If the Vaccine Isn’t Always Effective, Why Get One?

The flu is a serious illness. When the viruses in the vaccine are a good match with what’s circulating, the vaccine can reduce your risk of having the flu by 40%-60%. And even when the match isn’t great, being vaccinated before you get the flu can help you avoid having a severe case. Numerous studies have shown that the vaccine cuts your risk of having to go to the hospital -- and if you are hospitalized, you’re much less likely to be admitted to the intensive care unit.

According to the CDC’s estimates for the 2018-19 season, vaccinating only half of all Americans prevented 4.4 million cases of the flu, 58,000 hospitalizations, and 3,500 deaths. That was in a year that the vaccine was only 29% effective.

“Even with a less-than-perfect vaccine, there can still be big results in terms of prevented illnesses and severe outcomes,” says Petrie.

For children, the vaccine can be life-saving: A study of four flu seasons found that vaccination reduced the risk of death by half for kids with other conditions, and by almost two-thirds among healthy kids.

“We almost never know ahead of time whether we’ve guessed correctly or not. We can’t say, ‘This year it’s only going to be 10% effective, so don’t get it,’” says Jackson. “But the vaccine is relatively low-cost, with rare side effects, and reducing the risk of hospitalization and death by 50% is better than nothing.”

And much like wearing a mask helps protect those around you from the coronavirus, getting a flu shot may also help safeguard others who are more vulnerable to a severe case, like the very young and old and those with some chronic health conditions.

Improving the Flu Vaccine

Researchers are working to make the vaccine more effective on two fronts. Some are looking for ways to produce the annual vaccine more quickly, which would give scientists more time to pinpoint exactly which viruses to include. The longer they can wait, the more likely they are to make an accurate prediction.

Until 2013, all flu vaccines were made by growing samples of the viruses in fertilized chicken eggs, which required not only an enormous number of eggs but also lots of time. And growing the virus in eggs can introduce changes to it, which can make the vaccine less effective. But now, two other technologies can grow the virus faster.

Cell-based vaccines grow samples of the virus in cultured animal cells, which can take less time than using eggs. (The savings vary, but it starts with the fact that the cells are kept frozen in cell banks, so manufacturing doesn’t have to wait for a large supply of eggs.) And recombinant vaccines don’t need a sample at all. They use DNA to create a synthetic version of the viruses. Right now, there’s only one cell-based flu vaccine and one recombinant flu vaccine approved by the FDA. For the 2020-21 flu season, the CDC expects 81% of the vaccine supply to be egg-based.

The other way we could see an improvement is a bit of a vaccination holy grail: A universal flu vaccine, one that could provide long-lasting protection against many types of the virus. This would stop the need for a new version of the vaccine each year. Researchers have been working for years to create a vaccine that targets a stable portion of the virus -- one that doesn’t mutate. Several possible universal vaccines are in clinical trials right now, including three that have reached phase III, where the vaccine is given to thousands of people and tested to make sure it works and is safe.

"We're on the cusp of a universal flu vaccine," Amesh Adalja, MD, an infectious diseases specialist and senior scholar at Johns Hopkins Center for Health Security in Baltimore, told LiveScience. "It's long been a joke that a universal flu vaccine is always 5 years away. But I think, this time, it really is coming within the next 5 years."

Show Sources

National Library of Medicine: “Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010.”

CDC: “2018-19 Influenza Illnesses, Medical Visits, Hospitalizations, and Deaths Averted by Vaccination,” “Misconceptions about Seasonal Flu and Flu Vaccines,” “Vaccine Effectiveness: How Well Do the Flu Vaccines Work?” “CDC Seasonal Flu Vaccine Effectiveness Studies,” “Past Seasons Vaccine Effectiveness Estimates,” “Influenza Historic Timeline,” “Types of Influenza Viruses,” “Selecting Viruses for the Seasonal Influenza Vaccine,” “CDC Study Finds Flu Vaccine Saves Children’s Lives,” “How Influenza (Flu) Vaccines Are Made,” “Seasonal Influenza Vaccine Supply for the U.S. 2020-2021 Influenza Season.”

National Opinion Research Center (NORC) at the University of Chicago: “37% of Americans Do Not Plan to Get a Flu Shot This Season.”

Joshua Petrie, PhD, research investigator, Department of Epidemiology, University of Michigan School of Public Health.

Michael L. Jackson, PhD, associate investigator, Kaiser Permanente Washington Health Research Institute.

Jeffrey Shaman, PhD, professor, environmental health sciences, and director, climate and health program, Columbia University Mailman School of Public Health.

American Society for Microbiology: “A Universal Influenza Vaccine: How Close Are We?”

LiveScience: “Scientists may be 'on the cusp' of a universal flu vaccine.”

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