Vaccine Effectiveness: How Well Do Flu Vaccines Work?

How effective are flu vaccines?

CDC conducts studies each year to determine how well influenza (flu) vaccines protect against flu. While vaccine effectiveness (VE) can vary, recent studies show that flu vaccination reduces the risk of flu illness by between 40% and 60% among the overall population during seasons when most circulating flu viruses are well-matched to those used to make flu vaccines. In general, current flu vaccines tend to work better against influenza B and influenza A(H1N1) viruses and offer lower protection against influenza A(H3N2) viruses. Go to “Does flu vaccine effectiveness vary by type or subtype?” and “Why is flu vaccine typically less effective against influenza A H3N2 viruses?” for more information.

What are factors that influence how well flu vaccines work?

How well flu vaccines work (or their ability to protect against a certain outcome) can vary from season to season. Protection can vary depending on who is being vaccinated. At least two factors play an important role in determining the likelihood that vaccination will protect a person from flu illness: 1) characteristics of the person being vaccinated (such as their age and health), and 2) how well the vaccines “match” the flu viruses spreading in the community. When flu vaccines are not well matched to one or more circulating influenza viruses, it is possible that vaccination may provide little or no protection from illness caused by those viruses, but still provide protection against other flu viruses that circulate during the season. When there is a good match between flu vaccines and circulating viruses, vaccination provides substantial benefits by preventing flu illness and complications.

Each flu season, researchers try to determine how well flu vaccines work as a public health intervention. Estimates of how well a flu vaccine works can vary based on study design, outcome(s) measured, population studied and type of flu vaccine. Differences between studies must be considered when results are compared.

What are the benefits of flu vaccination?

Are flu vaccines effective against all types of flu and cold viruses?

Seasonal flu vaccines are designed to protect against infection and illness caused by the four flu viruses that research indicates will be most common during the upcoming flu season. Flu vaccines do not protect against infection and illness caused by other viruses that also can cause flu-like symptoms. There are many other viruses besides flu viruses that can result in flu-like illness* (also known as influenza-like illness or “ILI”) that spread during the flu season. These non-flu viruses include rhinovirus (one cause of the “common cold”) and respiratory syncytial virus (RSV), which is the most common cause of severe respiratory illness in young children, and a major cause of severe respiratory illness in adults 65 years and older.

Does flu vaccine effectiveness vary by type or subtype?

Yes. The amount of protection provided by a flu vaccine may vary by flu virus type or subtype or by vaccine, even when viruses used to make flu vaccines are similar (or ‘well matched’) to the influenza viruses that are causing illness that season. Since 2009, VE studies looking at how well flu vaccines protect against medically attended illness have suggested better protection against influenza B or influenza A(H1N1) viruses than against influenza A(H3N2) viruses. A study [505 KB, 10 pages] that looked at a number of VE estimates from 2004-2015 found average VE of 33% (CI = 26%–39%) against illnesses caused by H3N2 viruses, compared with 61% (CI = 57%–65%) against H1N1 and 54% (CI = 46%–61%) against influenza B virus illnesses. VE estimates were lower when viruses used to make vaccines were different (not well-matched) from the flu viruses causing illness that season, especially against A(H3N2) viruses. The same study found average VE of 23% (95% CI: 2% to 40%) against A(H3N2) viruses when circulating influenza viruses were not well-matched to the A(H3N2) viruses used to make that season’s flu vaccines.

Why is flu vaccine typically less effective against influenza A(H3N2) viruses?

There are a number of reasons why flu vaccine effectiveness against influenza A(H3N2) viruses may be lower.

1. While all flu viruses undergo frequent genetic changes, the changes that have occurred in influenza A(H3N2) viruses have more frequently resulted in differences between the virus components of the flu vaccine and circulating influenza viruses (i.e., antigenic change) compared with influenza A(H1N1) and influenza B viruses. That means that between the time when flu viruses are selected to begin producing vaccines and when flu vaccines are delivered, A(H3N2) viruses are more likely than A(H1N1) or influenza B viruses to have changed in ways that could impact how well the flu vaccines work.
2. Growth in eggs is part of the production process for most seasonal flu vaccines. While all influenza viruses undergo changes when they are grown in eggs, changes in influenza A(H3N2) viruses tend to be more likely to result in antigenic changes compared with changes in other influenza viruses. These so-called “egg-adapted changes” are present in vaccine viruses recommended for use in vaccine production and may reduce their potential effectiveness against circulating influenza viruses. Other vaccine production technologies, e.g., cell-based vaccine production or recombinant flu vaccines, do not use eggs in vaccine production to avoid egg-adapted changes to the viruses used to make vaccines. CDC also is using advanced molecular techniques to improve flu vaccines.

How effective are flu vaccines in older adults?

In numerous studies since 2010, flu vaccines have helped protect older adults against influenza. Flu vaccination has reduced the risk of medically attended illness caused by A(H1N1) or influenza B viruses by more than 60% among people 65 years and older (1). Flu vaccines also have reduced the risk of flu hospitalization among adults 65 years and older due to A(H1N1) and influenza B(2). However, protection against influenza A(H3N2) viruses has been less consistent. On average, flu vaccines have reduced the risk of doctor visits for people with A(H3N2) flu by 24% and reduced the risk of hospitalization with A(H3N2) flu by 33% in adults 65 years and older (1,2). During seasons when the H3N2 vaccine component has been well-matched to the flu viruses circulating in the community, the benefit from flu vaccination has been higher. During these seasons, flu vaccine reduced the risk of hospitalization with A(H3N2) flu by 43% on average (2). But when the vaccine component was less similar to viruses in the community, the protection has dropped to 14% (2).For older adults, some studies have shown that some newer vaccines (the high-dose inactivated vaccine, the adjuvanted inactivated vaccine, and the recombinant influenza vaccine) might be more effective than standard-dose inactivated vaccines without an adjuvant. Because flu viruses and effectiveness of flu vaccines can vary from one season to another, it isn’t known whether any one of these vaccines will always be more effective in every flu season.

For the 2022-2023 flu season, CDC and the Advisory Committee on Immunization Practices (ACIP) have made a preferential recommendation for higher dose and adjuvanted flu vaccines for people aged 65 years and older. The preference applies to Fluzone High-Dose Quadrivalent vaccine, Flublok Quadrivalent recombinant flu vaccine and Fluad Quadrivalent adjuvanted flu vaccines. This recommendation was based on a review of available studies which suggests that, in this age group, these vaccines are potentially more effective than standard dose unadjuvanted flu vaccines. If one of the three preferentially recommended flu vaccines for people 65 and older is not available at the time of administration, people in this age group should get an age-appropriate standard-dose flu vaccine instead.

1. 1. Edward A. Belongia, Danuta M. Skowronski, Huong Q. McLean et al. Repeated annual influenza vaccination and vaccine effectiveness: review of evidence. Expert Review of Vaccines. 2017 Jun; 16(7): 723-36. doi: 10.1080/14760584.2017.1334554.
   2. Marc Rondy, Nathalie El Omeiri, Mark G. Thompson, et al. Effectiveness of influenza vaccines in preventing severe influenza illness among adults: A systemic review and meta-analysis of test-negative design case-control studies. Journal of Infection. Sept 2017; 65: 381-394. doi: 10.1016/j.jinf.2017.09.010

If older people have weaker immune responses to flu vaccination, should they still get vaccinated?

Despite the fact that some older adults (people 65 years and older) have weaker immune responses to the influenza A(H3N2) component of flu vaccines, there are many reasons why people in this age group should be vaccinated each year.

• First, people 65 years and older are at increased risk of serious illness, hospitalization and death from flu.
• Second, while the effectiveness of flu vaccines can be lower among some older people (particularly against influenza A(H3N2) viruses), there are seasons when significant benefit can be observed (this is particularly true against influenza A(H1N1) and influenza B viruses).
• Third, flu vaccination has been shown in several studies to reduce severity of illness in people who get vaccinated but still get sick.
• Flu vaccines can protect against more serious outcomes like hospitalization and death. For example, one study concluded that one death was prevented for every 4,000 people vaccinated against flu (1).
• Fourth, in adults 65 years and older, hospitalizations can mark the beginning of a significant decline in overall health and mobility, potentially resulting in loss of the ability to live independently or to complete basic activities of daily living. While the protection older adults obtain from flu vaccination can vary significantly, a yearly flu vaccination is still the best protection currently available against flu.
• In addition, it’s important to remember that people who are 65 and older are a diverse group and often are different from one another in terms of their overall health, level of activity and mobility, and behavior when it comes to seeking medical care. This group includes people who are healthy and active and have responsive immune systems, as well as those who have underlying medical conditions that may weaken their immune system and their bodies’ ability to respond to vaccination. Therefore, when evaluating the benefits of flu vaccination, it is important to look at a broader picture than what one study’s findings can present.

1. Fireman B, Lee J, Lewis N et al. Influenza vaccination and mortality: differentiating vaccine effects from bias. Am J Epidemiol. 2019 Sep; 170(5): 650-6. doi: 10.1093/aje/kwp173.

How effective are flu vaccines in children?

Vaccination has been found during most seasons to provide a similar level of protection against flu illness in children to that seen among adults.

In several studies, flu vaccine effectiveness was higher among children who received two doses of flu vaccine the first season that they were vaccinated (as recommended) compared to “partially vaccinated” children who only received a single dose of flu vaccine. However, in some seasons, partially vaccinated children still receive some protection.

In addition to preventing illness, flu vaccine can prevent severe, life-threatening complications in children, for example:

• A 2014 study showed that flu vaccine reduced children’s risk of flu-related pediatric intensive care unit (PICU) admission by 74% during flu seasons from 2010-2012.
• In 2017, a study in the journal Pediatrics was the first of its kind to show that flu vaccination also significantly reduced a child’s risk of dying from flu. The study, which looked at data from four flu seasons between 2010 and 2014, found that flu vaccination reduced the risk of flu-associated death by half (51 percent) among children with underlying, higher risk medical conditions and by nearly two-thirds (65 percent) among healthy children.

How are benefits of vaccination measured?

Public health researchers measure how well flu vaccines work through different kinds of studies. In “randomized studies,” flu vaccination is randomly assigned, and the number of people who get flu in the vaccinated group is compared to the number who get flu in the unvaccinated or placebo group. Randomized studies are the “gold standard” (best method) for determining how well a vaccine works. The effects of vaccination measured in these studies is called “vaccine efficacy.” Randomized, placebo-controlled studies are expensive and are not conducted after a recommendation for vaccination has been issued, as withholding vaccine from people recommended for vaccination would place them at risk for infection, illness and possibly serious complications. For that reason, most U.S. studies of vaccine benefits conducted after a vaccine is licensed and recommended are “observational studies.” Observational studies look at a group of people in a real world setting and compare the occurrence of flu illness in vaccinated people to unvaccinated people. This means that vaccination of study subjects is not randomized. The measurement of vaccine effects in an observational study is referred to as “vaccine effectiveness.”

How does CDC measure how well flu vaccines work?

CDC typically presents vaccine effectiveness (VE) as a single point estimate: for example, 60%. This point estimate represents the reduction in risk provided by a flu vaccine. CDC vaccine effectiveness studies measure different outcomes. For example, outcomes measured can include laboratory-confirmed flu illness (that results in a doctor’s visit), hospitalizations or intensive care unit (ICU) admissions. For these outcomes, a VE point estimate of 60% means that on average the flu vaccine reduces a person’s risk of that flu outcome by 60%.

In addition to the VE point estimate, CDC also provides a “confidence interval” (CI) for this point estimate, for example, 60% (95% CI: 50%-70%). The confidence interval provides a lower boundary for the VE estimate (e.g., 50%) as well as an upper boundary (e.g., 70%). One way to interpret a 95% confidence interval is that if CDC were to repeat this study 100 times , 95 times out of 100, the confidence interval would contain the true VE value. Another way to look at this is that there is a 95% chance that the true VE lies within the range described by the confidence interval. This means there is still the possibility that five times out of 100 (a 5% chance) the true VE value could fall outside of the 95% confidence interval.

Why are confidence intervals important for understanding flu vaccine effectiveness?

Confidence intervals are important because they provide context for understanding the precision or exactness of a VE point estimate. The wider the confidence interval, the less exact the point value estimate of vaccine effectiveness becomes. Take, for example, a VE point estimate of 60%. If the confidence interval of this point estimate is 50%-70%, then we can have greater certainty that the true protective effect of the flu vaccine is near 60% than if the confidence interval were between 10% and 90%. Furthermore, if a confidence interval crosses zero, for example, (-20% to 60%), then the point value estimate of VE provided is considered “not statistically significant.” People should be cautious when interpreting VE estimates that are not statistically significant because such results cannot rule out the possibility of zero VE (i.e., no protective benefit). The width of a confidence interval is related in part to the number of participants in the study, and so studies that provide more precise estimates of VE (and consequently, have a narrower confidence interval) typically include a larger number of participants.

Is it true that getting vaccinated repeatedly can reduce vaccine effectiveness?

A report examining studies from the 2010-2011 to the 2014-2015 seasons concluded that the effectiveness of a flu vaccine may be influenced by vaccination the prior season or during many prior seasons (1,2). In some seasons, protection against influenza A(H3N2) virus illness may have been lower for people vaccinated in the current season and the prior season compared with those who had only been vaccinated in the current season. This fits with findings on immune response to vaccination that suggest repeated influenza vaccination can weaken the immune response to vaccination and especially to the H3N2 vaccine component. However, repeated annual vaccination also can be beneficial during some seasons, since sometimes people retain and carry over immune protection from one season to the next. During some seasons, people who missed getting vaccinated still had residual protection against influenza illness.

Information regarding flu vaccination history is particularly important to these types of evaluations, and can be difficult to confirm, as accurate vaccination records are not always readily available. People who choose to get vaccinated every year may have different characteristics and susceptibility to flu compared to those who do not seek vaccination every year. CDC supports continued efforts to monitor the effects of repeat vaccination each year in part to understand the immune response to repeat vaccination better. However, based on the substantial burden of flu in the United States, and on the fact that most studies point to vaccination benefits, CDC recommends that yearly flu vaccination is the first and most important action people can take to protect against flu and its potentially serious complications.

1. Edward A. Belongia, Danuta M. Skowronski, Huong Q. McLean et al. Repeated annual influenza vaccination and vaccine effectiveness: review of evidence. Expert Review of Vaccines. 2017 Jun; 16(7): 723-36. doi: 10.1080/14760584.2017.1334554.
2. Kim SS, Flannery B, Foppa IM, Chung JR, Nowalk MP, Zimmerman RK, Gaglani M, Monto AS, Martin ET, Belongia EA, McLean HQ, Jackson ML, Jackson LA, Patel M. Effects of Prior Season Vaccination on Current Season Vaccine Effectiveness in the United States Flu Vaccine Effectiveness Network, 2012-2013 Through 2017-2018. Clin Infect Dis. 2021 Aug 2;73(3):497-505. doi: 10.1093/cid/ciaa706. PMID: 32505128; PMCID: PMC8326585.

Why are there so many different outcomes for vaccine effectiveness studies?

Vaccine effectiveness studies that measure different outcomes are conducted to better understand the different kinds of benefits provided by vaccination. Ideally, public health researchers want to evaluate the benefits of vaccination against illness of varying severity.  To do this, they assess how well flu vaccines work to prevent illness resulting in a doctor visit, or illness resulting in hospitalization, ICU admission, and even death associated with flu. Because estimates of vaccine effectiveness may vary based on the outcome measured (in addition to season, population studied, and other factors), results should be compared between studies that used the same outcome for estimating vaccine effectiveness.

How does CDC measure how well the vaccine works?

Scientists continue to work on better ways to design, conduct and evaluate non-randomized (i.e., observational) studies to assess how well flu vaccines work. CDC has been working with researchers at universities and hospitals since the 2003-2004 flu season to estimate how well flu vaccine works through observational studies using laboratory-confirmed flu as the outcome. These studies currently use a very accurate and sensitive laboratory test known as real-time RT-PCR (reverse transcription polymerase chain reaction) to confirm medically attended flu virus infections as a specific outcome. CDC’s studies are conducted in sites located across the United States to gather data that accurately represents people and conditions across the country. To assess how well the vaccine works across different age groups, CDC’s studies of flu vaccine effects have included all people aged 6 months and older recommended for an annual flu vaccination. Similar studies are being done in Australia, Canada and Europe.

Over the past few years, CDC has conducted VE studies using multiple networks, including the U.S. Flu VE Network, the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN), the Influenza and Other Viruses in the Acutely Ill (IVY) network, the National Vaccine Surveillance Network (NVSN), and the VISION VE Network. For this upcoming winter, HAIVEN will no longer be used. HAIVEN looked at how well flu vaccines protect against flu-related hospitalization among adults aged 18 and older. HAIVEN ended enrollment on July 31, 2021, but CDC will continue to collect information on adults hospitalized with flu through its other VE networks, including IVY and VISION. IVY consists of 21 large, adult hospitals in 20 U.S. cities and was originally created in 2019 to estimate how well the flu vaccine works at preventing severe flu illness among intensive care unit (ICU) patients. As of April 1, 2021, IVY has expanded to enroll all adults hospitalized with COVID-19. During the 2021-2022 flu season, the network will also enroll patients hospitalized with flu. NVSN collects vaccine effectiveness data on pediatric hospitalizations with laboratory confirmed flu in children 18 years of age and younger. The VISION VE Network collects data on emergency department visits, hospitalizations, and intensive care unit (ICU) admissions. The network was established in 2019 and includes the following eight U.S. sites:

• Baylor Scott and White Health (BSHW; Texas)
• Columbia University Irving Medical Center (CUIMC; New York)
• HealthPartners (HP; Minnesota and Wisconsin)
• Intermountain Healthcare (IH; Utah)
• Kaiser Permanente Northern California (KPNC; California)
• Kaiser Permanente Northwest (KPNW; Oregon and Washington)
• Regenstrief Institute (RG; Indiana)
• University of Colorado (UCO; Colorado).

What do recent vaccine effectiveness studies show?

Recent studies show flu vaccine can reduce the risk of flu illness by between 40% and 60% among the overall population during seasons when most circulating flu viruses are well matched to the flu vaccine viruses.

Do recent vaccine effectiveness study results support flu vaccination?

The large numbers of flu-associated illnesses and deaths in the United States, combined with the evidence from many studies that show flu vaccines help to protect against flu illness and its potentially serious complications, support the current U.S. flu vaccination recommendations. CDC recommends a yearly flu vaccine as the first and most important step in protecting against flu viruses. Everyone 6 months and older should get an annual flu vaccine, ideally by the end of October.

Where can I get more information?

CDC has compiled a list of selected publications related to vaccine effectiveness.

Besides vaccination, how can people protect themselves against the flu?

Getting a flu vaccine each year is the best way to prevent the flu. In addition to getting the flu shot, people should take the same everyday preventive actions to prevent the spread of flu, including covering coughs, washing hands often, and avoiding people who are sick. Antiviral drugs are an important second line of defense to treat the flu. These drugs are not a substitute for vaccination and must be prescribed by a health care provider.

More information on Vaccine Selection.