Flu Vaccine Effectiveness

A flu shot can greatly reduce your risk of getting the flu; image by Getty Images.

Influenza (flu) vaccines are nasal sprays or injections currently composed either of live attenuated (rendered much less able to cause infection) flu viruses or killed viruses or virus components (both are unable to reproduce) that, when administered to individuals, generate an immune response that will be strong enough to protect that individual from developing influenza disease. The design of the vaccine depends on how health care providers usually administer it; health care professionals usually administer the live attenuated vaccine by a nasal spray (intranasal), while health care providers typically administer the killed virus by an intramuscular injection (shot), usually into the deltoid (arm) muscle. People cannot get the flu from the injected vaccine because the vaccine contains no live virus. However, nasal sprays use attenuated viruses (meaning that the viruses are live but cannot effectively cause disease) that, in some people (immunosuppressed people), may cause mild flu-like symptoms. Note that health care providers previously did not recommend nasal sprays because of poor immune responses in people as compared to those who get the shots. However, in 2018, health care professionals approved the improved nasal sprays for use in some individuals (see below).

Facts

• Flu vaccines can be quite different based on the viral type (or strains of the flu virus) used to make the vaccine. For example, seasonal vaccines usually are now made up of a combination of three or four different influenza viruses (flu strains that differ in some of their surface molecules), also termed as three or four-component vaccines. Experts choose the viruses in each year's vaccine because the chosen strains represent the most likely viruses to emerge in an upcoming flu season.
• Pandemic flu vaccines are created in response to a specific strain of flu virus that is causing widespread disease. They differ from seasonal vaccines in several ways. First, health researchers usually made the vaccines from new flu virus, not detected in previous flu seasons by flu experts and not included in the seasonal flu vaccines. These flu viruses are usually so new that most human immune systems do not easily recognize them, allowing viruses to quickly spread globally. Pandemic flu vaccines contain only a single strain of the pandemic virus (for example, H1N1 virus) instead of the usual three or four flu types used in a seasonal vaccine mixture. Seasonal vaccines are synthesized and distributed before the start of flu season (designated as Oct. 4 each year until May of the following year) while pandemic vaccines, unfortunately, have to be synthesized and distributed only after the pandemic virus has been identified and started its global spread.
• Until 2013, health researchers made all commercially available flu vaccines from viruses cultivated in chicken eggs and then collected, purified, tested for safety and efficacy, and once approved, distributed to care providers. This process usually takes about six months to accomplish, which gives a pandemic flu virus a long time to circulate and infect populations before researchers can develop a vaccine. In 2013, Flublok was approved for use; this vaccine is a trivalent vaccine made from insect cells (cell-based) that have recombinant DNA that produces viral proteins in an egg-free system (the egg-free system avoids problem of egg allergy in some patients). Researchers may synthesize future vaccines differently like Flublok. Current techniques are time-consuming, expensive, and yield vaccines that usually protect against only those viral strains present in the vaccine; the protection does not extend to the wide spectrum of flu virus strains. This limited protection is the reason that health researchers develop new flu vaccines each year.

In 1933, researchers discovered that viruses (influenza virus types A, B, and rarely C) cause influenza (flu). Prior to 1933, people thought a bacterium named Haemophilus influenzae caused the flu. In 1938, Jonas Salk and Thomas Francis developed the first vaccine against flu viruses. This first flu vaccine protected the U.S. military forces against the flu during World War II. Dr. Salk used his experience with influenza vaccine to develop an effective polio vaccine in 1952. Vaccines produced from the 1940s to the 1960s were not as purified as more modern vaccines, and the impurities in vaccines were thought to contribute to side effects such as fever, aches, and fatigue. Since these symptoms were similar to those that accompanied the flu (flu symptoms usually were more severe and lasted longer), people mistakenly thought they got the flu from the vaccination. However, they did not get the flu from the vaccines since the vaccines used killed virus.

In a public vaccination program designed to prevent a pandemic swine flu outbreak in 1979, about 25% of people in the United States received flu vaccinations. Unfortunately, the 1979 vaccine was associated with a small increased risk of Guillain-Barré syndrome, a serious neurological condition, with the risk estimated to be one to nine excess cases per million doses of vaccine, but no cause for this increase in risk was ever discovered. Fortunately, no pandemic developed, and the vaccination program for that flu virus was cancelled. Since that time, researchers have improved vaccine purification, and millions of people have continued to be vaccinated every year. Currently, influenza viruses are inoculated into eggs, where they multiply; afterward, they are harvested and separated from most egg particles and egg antigens, but some people who have an egg allergy may get a reaction to such a flu vaccination; however, most people who have a mild egg allergy usually have no reaction to the vaccines. Attenuated viruses (for nasal sprays like FluMist) are grown similarly, but strains are selected that only replicate under cool or cold temperatures so they can survive in the cool nasal passages long enough to stimulate an immune response but do not easily replicate and spread to warmer body regions like the lungs.

Because of the potential for widespread infection, life-threatening complications, and deaths that the H1N1 pandemic virus strain seemed to possess, health researchers accelerated the H1N1 tests so that the vaccine could be provided before the usual six-month timeline. However, all of the steps (cultivation, safety, efficacy, approval, and distribution) were done in the same way as for seasonal vaccines but over a shorter period with fewer people involved in the initial trials. Tested and approved H1N1 vaccine started to become available in late September 2009 (in Europe) and in October 2009 in the Americas and Asia.

A major change in terminology (naming conventions or abbreviations for influenza vaccines) occurred in the 2014-2015 vaccine year. Since then, vaccine abbreviations have continued to change. The new terminology (abbreviations) are as follows, according to the CDC established in 2019-2020:

• IIV = Inactivated Influenza Vaccine
  • IIV3 = Trivalent Inactivated Influenza Vaccine
  • IIV4 = Quadrivalent Inactivated Influenza Vaccine
• RIV4 = Quadrivalent Recombinant Influenza Vaccine
• LAIV4 = Quadrivalent Live Attenuated Influenza Vaccine
• aIIV3 refers specifically to adjuvanted IIV3
• ccIIV4 refers specifically to cell-culture based IIV4
• HD-IIV3 refers specifically to high-dose IIV3
• SD-IIV3 and SD-IIV4 refer specifically to standard-dose IIVs

Although only a few different influenza virus strains circulate in human populations at any given time, people may continue to become ill with the flu throughout their lives. The reason for this continuing susceptibility is that the eight RNA strands that comprise the influenza virus genome are continually mutating through the mechanisms of antigenic shift and drift. Antigenic drift is a series of mutations that occurs over time and causes a gradual evolution of the virus. Antigenic shift is an abrupt change in the RNA genome that usually results in significant changes in the hemagglutinin and/or the neuraminidase proteins (surface components of the flu virus). In this case, a new subtype of the virus suddenly emerges. Influenza A virus mutates the most with both of the mechanisms, while influenza B changes mainly by the slower process of antigenic drift and doesn't cause pandemics like influenza A.

Each year, health researchers update the seasonal vaccine to include the most current influenza virus strains that are infecting people worldwide. The fact that influenza viral genes continually change is one of the reasons people must get a flu vaccine every year, because often the immune response to one flu viral strain will not protect against other flu strains. Another reason is that antibodies produced by the host in response to the vaccine decline over time, and antibody levels are often low one year after vaccination. However, within about two weeks of receiving the vaccine, most people are protected against the viral strains that compose the vaccine. Vaccines produce immunity that lasts for at least a year; some people are protected by the vaccine against the strains of viruses for many years. Although most individuals need only one vaccine administration (flu shot) per year, the Centers for Disease Control and Prevention (CDC) recommends that children aged 6 months to 8 years obtain two doses. Please see the section on viral strains and vaccine producers in this article for the current composition of flu strains used in the 2020-2021 seasonal flu vaccines; however, if you have any questions, please check any CDC updates that may happen during the flu season.

The CDC recommends that anyone (except for certain groups, see below and people allergic to eggs) over 6 months of age be vaccinated against the flu. This is particularly important for certain people, including those who are at high risk of having serious seasonal flu-related complications or people who live with or care for those at high risk for serious seasonal flu-related complications. During flu seasons when vaccine supplies are limited or delayed, the Advisory Committee on Immunization Practices (ACIP) makes recommendations regarding priority groups for vaccination. The most recent ACIP recommendations presented by the CDC for 2020-2021 are as follows:

• Routine annual influenza vaccination is recommended for all people aged ≥6 months who do not have contraindications.
• A licensed, age-appropriate influenza vaccine (IIV, RIV4, or LAIV4) should be used.
• Emphasis should be placed on vaccination of high-risk groups and their contacts/caregivers. When vaccine supply is limited, vaccination efforts should focus on delivering vaccination to (no hierarchy implied by order listed) the following:
  • Children aged 6-59 months
  • Adults aged ≥50 years
  • People with chronic pulmonary (including asthma), cardiovascular (excluding isolated hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus)
  • People who are immunocompromised due to any cause, (including medications or HIV infection)
  • Women who are or will be pregnant during the influenza season
  • Children and adolescents (aged 6 months through 18 years) receiving aspirin- or salicylate-containing medications and who might be at risk for Reye syndrome
  • Residents of nursing homes and other long-term care facilities
  • American Indians/Alaska natives
  • People who are extremely obese (BMI ≥40)
  • Caregivers and contacts of those at risk:
    • Health care personnel in inpatient and outpatient care settings, medical emergency-response workers, employees of nursing home and long-term care facilities who have contact with patients or residents, and students in these professions who will have contact with patients;
    • Household contacts and caregivers of children aged ≤59 months (for example, <5 years), particularly contacts of children aged <6 months, and adults aged ≥50 years; and
    • Household contacts and caregivers of people with medical conditions that put them at high risk of severe complications from influenza.

There is a high-dose IM vaccine for people 65 and older (contains more viral antigen to stimulate the possibly less responsive immune system in people age 65 and older).

Healthy people 2-49 years of age who are not pregnant may get the nasal spray vaccine. The term FluMist is another name for the seasonal flu nasal spray vaccine. LAIV4 does not contain thimerosal or other preservatives. According to the CDC, the following people should not get the nasal-spray vaccine and note current CDC recommendations:

• People less than 2 years of age
• People 50 years of age and over
• People with a medical condition that places them at high risk for complications from influenza, including those with chronic heart disease like history of a heart attack or lung disease, such as asthma or reactive airways disease
• People with medical conditions such as diabetes or kidney failure
• People with illnesses that weaken the immune system or who take medications that can weaken the immune system
• Children <5 years of age with a history of recurrent wheezing
• Children or adolescents receiving aspirin therapy
• People with a history of Guillain-Barré syndrome that occurred after receiving influenza vaccine
• Pregnant women
• People who are allergic to any of the components of the nasal-spray vaccine
• It is important to note that if the vaccine's recipient sneezes immediately after administration, the dose should not be repeated.

In addition, the package insert states that people allergic to gentamicin (Gentak, Garamycin), arginine, or gelatin should not use the nasal spray. These recommendations also apply to the new quadrivalent vaccines. However, because of the poor performance as a vaccine, the CDC has not recommended the nasal mist vaccine for the last few years; however, in 2020, this recommendation was changed.

Please see the two extensive tables in reference 1 for details about all vaccines approved for use in the United States against the flu for the 2020-2021season. You should discuss which flu vaccine is best for you with your doctor.

In general, all medications, including intramuscular and nasal-spray vaccines, have side effects and the potential for allergic reactions. For most medicines and vaccines, the side effects or reactions are infrequent and are minimal if they do occur. Consequently, the pros far outweigh the cons for vaccination. The seasonal and pandemic vaccines are no different. What is different about the side effects of flu vaccines is that the occasional side effects seen with all flu vaccines usually resemble the flu disease. About 5%-10% of people experience mild side effects, such as headache, nasal congestion, low-grade fever, sore throat, or muscle cramps. Some individuals may experience short-term (hours to about a day) dizziness, nausea, and/or soreness or a mild rash at the inoculation site as vaccination side effects. Although these are short-lived, some people think they contracted the flu from the vaccine. This is a myth. The intramuscular vaccines contain no live virus, so the vaccine cannot transmit the disease. Although the nasal-spray vaccines contain live virus, it contains weakened (attenuated) virus. The vast majority of attenuated viruses (altered so they will not replicate or do so poorly) will not be able to cause influenza in people with normal immune systems and good health because the attenuated viruses replicate poorly or not at all in these people. These side effects are most likely to occur in children who have not been exposed to influenza virus in the past, but they can occur in some adults.

About one-third or fewer of those vaccinated develop soreness and occasional redness at the injection site. Allergic reactions are rare. Intramuscular vaccine shots are usually mildly painful when injected into muscle tissue.

Flu vaccine effectiveness is judged by the ability of the vaccine to generate an immune response (measured by a blood test known as a hemagglutination-inhibition assay; protection is deemed effective if assay titer of antibodies reaches 1:40 or greater). This applies to both seasonal and pandemic flu vaccines. A titer of 1:40 is considered to be protective 21 days after vaccination. Vaccine efficacy also varies from one person to another; one person's titer could be different from another person's titer, even if both were given vaccine from the same batch.

Previous studies of healthy young adults have shown influenza seasonal vaccine to be 70%-90% effective in preventing illness. In the elderly and those with certain chronic medical conditions such as HIV, the vaccine is often less effective in preventing illness. However, studies show the vaccine reduces hospitalization by about 70% and death by about 85% among the elderly who are not in nursing homes. Among nursing home residents, vaccine can reduce the risk of hospitalization by about 50%, the risk of pneumonia by about 60%, and the risk of death by 75%-80%.

However, experience with the vaccine, studied each year, can show a wide variation in effectiveness. The 2014-2015 vaccine demonstrated this point. Health researchers designed the vaccine to protect against those major flu viruses that emerged in 2014. Unfortunately, new strains arose in late 2014 so that the vaccine synthesized for the 2014-2015 season was only about 23% effective. However, the CDC still recommended utilization of the vaccine, as it seemed to reduce the severity of the flu in people who were vaccinated but still became infected with the flu virus.

The American Academy of Pediatrics (AAP) recommends that children all children 6 months and older receive a seasonal flu vaccine (some children under the age of 9 will need two doses). AAP and others recommend both inactivated influenza vaccine (IIV) and live attenuated influenza vaccine (LAIV) as vaccine options for the 2020-2021 season with no preference. For additional information, see https://www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/immunizations/Influenza-Implementation-Guidance/Pages/Annual-AAP-Influenza-Policy.aspx or your child's doctor.

The FDA, CDC, and other institutions in the U.S. continuously monitor the effectiveness and safety of vaccines, and recommendations may change.

The following changes and updates are taken from the first reference from the CDC:

The composition of the 2020-21 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B/Victoria lineage components. These updated components will be included in both trivalent and quadrivalent vaccines. Quadrivalent vaccines will include an additional influenza B virus component from the B/Yamagata lineage, which is unchanged from that included in quadrivalent influenza vaccines used during the 2019-20 season. For the 2020-21 season, U.S. egg-based influenza vaccines (for example, vaccines other than ccIIV4 and RIV4) will contain hemagglutinin (HA) derived from an influenza A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09-like virus, an influenza A/Hong Kong/2671/2019 (H3N2)-like virus, an influenza B/Washington/02/2019 (Victoria lineage)-like virus, and (for quadrivalent egg-based vaccines) an influenza B/Phuket/3073/2013 (Yamagata lineage)-like virus. U.S. cell culture-based inactivated (ccIIV4) and recombinant (RIV4) influenza vaccines will contain HA derived from an influenza A/Hawaii/70/2019 (H1N1)pdm09-like virus, an influenza A/Hong Kong/45/2019 (H3N2)-like virus, an influenza B/Washington/02/2019 (Victoria lineage)-like virus, and an influenza B/Phuket/3073/2013 (Yamagata lineage)-like virus.

Two new influenza vaccine licensures are described:

In November 2019, FDA licensed Fluzone High-Dose Quadrivalent (HD-IIV4). Fluzone High-Dose Quadrivalent is approved for use in persons aged ≥65 years. For the 2020-21 season, Fluzone High-Dose Quadrivalent is expected to replace the previously available trivalent formulation of Fluzone High-Dose (HD-IIV3). The dose volume for Fluzone High-Dose Quadrivalent (0.7 mL) is slightly higher than that of trivalent Fluzone High-Dose (0.5 mL). Fluzone High-Dose Quadrivalent, like Fluzone High-Dose, contains four times the amount of HA per vaccine virus in each dose compared with standard-dose inactivated influenza vaccines (60 µg per virus, versus 15 µg in standard-dose IIVs).

A summary of 2020-2021vaccines is available in an extensive table at https://www.cdc.gov/flu/professionals/acip/2020-2021/acip-table.htm.

Caregivers are strongly advised to read the package inserts to check for indications and contraindications before administering any type of vaccine, especially new vaccines, as sometimes the indications for use and contraindications change. Some vaccines have additional names like Fluad (Seqirus), Fluzone (Fluzone High-Dose), Fluarix, and others. In addition, the CDC occasionally makes updates about who should get what type of vaccine.

In August 2014, the FDA approved use of a jet injector for flu vaccination. The jet injector uses high-pressure fluid to penetrate the skin instead of a hypodermic needle and can be powered by gas or springs. Certain vaccine preparations (Afluria) may be used in the injector and can be used in people 18-64 years of age.

Thimerosal is a preservative that contains mercury. Multidose vials of conventional and pandemic flu vaccines often contain thimerosal to prevent contamination when the vial is repeatedly used to extract the vaccine. Although thimerosal is being phased out as a vaccine preservative, it is still used in flu vaccines in low levels. There is no data that indicate thimerosal in these vaccines has caused autism or other problems in individuals. Consequently, the FDA has indicated the following:

• There is no convincing evidence of harm caused by the small doses of thimerosal preservative in influenza vaccines, except for minor effects like swelling and redness at the injection site.
• A study of influenza vaccination examining over 2,000 pregnant women demonstrated no adverse fetal effects associated with influenza vaccine.

However, single-dose vials and the nasal-mist formulations of both the seasonal and pandemic vaccines contain no thimerosal. These vaccine options are available to individuals who still want thimerosal-free vaccine. For thimerosal levels in flu vaccines, the reader should see the CDC table in the reference under "mercury content."

The best chance for protection against seasonal (conventional) and pandemic flu is vaccination. The value of vaccination is very high for many individuals and even for the world's population. For individuals, seasonal flu often causes about 12,000 to 56,000 deaths in the U.S., with about 140,000 to 710,000 people hospitalized every year. There are from 9.2 million to 35.6 million flu illnesses in the U.S. population gets the seasonal flu each year and misses school, work, and vacation time, while productivity nationwide can decline. Seasonal flu takes the lives of our population 65 years of age and older; about 90%-95% of seasonal flu deaths occur in this age group. Without yearly seasonal flu vaccine, the illness and death rates would likely be much higher.

Pandemic flu in some instances can be far worse on world populations than seasonal flu. For example, the Spanish flu or 1918 flu pandemic killed about 45 million to 100 million people from 1918-1920. Commerce, economic systems, and travel were shut down in many areas of the world for months at a time during those years. In the recent H1N1 pandemic that began in Mexico in April 2009, the disease caused deaths "out of the usual flu season" and caused a shutdown in travel to Mexico that brought the country economic hardship. For many individuals, pandemic H1N1 flu was just a nuisance that makes people feel feverish and tired with sneezing and coughing that lasts for about a week; they recovered without any problems. For others, the pandemic H1N1 flu was disastrous and deadly. The H1N1 virus has behaved quite differently from the seasonal flu. It began in April 2009 (near the end of the seasonal flu season) and spread worldwide by September. H1N1 flu affected a different population than the seasonal flu. It caused the hospitalization and deaths of a markedly younger population (pediatric population, pregnant individuals, and young adults). Worldwide, H1N1 vaccine became available in limited amounts in late September and early October 2009. The H1N1 vaccine was initially given to those people at highest risk for complications (pediatric/children, pregnant women, caregivers). Researchers suggest the H1N1 vaccine was effective in reducing the effects of this flu virus, even though it was not as deadly as first estimated.

Vaccination against seasonal flu and the infrequent pandemic flu (1918 [no vaccine], 1957, 1968, and 2009) has been improved since it was first tried in the 1940s. Vaccination provides the best chance (about 70%-90%) to prevent the symptoms and complications (including pneumonia) of influenza infection from developing; the value of vaccinations is in the numbers of people who live and do not get sick from the disease as a result of their successful vaccination.

About 80% of the 172 children who died from the flu in 2017 did not receive the flu vaccine.

In the future, researchers may make vaccines differently; however, the vaccine hastily made in 2009 to protect people from H1N1 was deemed successful and can serve as a vaccine synthesis method until newer and faster vaccine synthesis methods are widely accepted.

Seasonal vaccines are usually available at most physician offices, urgent care clinics, and in the past few years, from some pharmacies (usually associated with pharmacy chains and grocery stores). Availability for the new flu seasonal vaccine starts in the late summer or early fall and if demand is normal, supplies are available well into the spring of the following year. This is not the situation for pandemic flu. As seen with the 2009 H1N1 pandemic, vaccine was not readily available and was rationed out to specific distribution sites that were tasked to vaccinate the most susceptible individuals initially until vaccine production was adequate to allow broad distribution. It is possible such circumstances could reoccur. If you need or want a specific vaccine, it is best to call the clinic, doctor's office, pharmacy or other health care professional to determine if the vaccine you want is available.

In fact, another influenza A H3N2v strain was noted in 2012 to be transmitted from pigs to humans. Fortunately, it causes symptoms similar to the seasonal flu, but there is no current development into a strain that easily transmits from person to person.

There are many researchers looking for ways to protect humans with vaccines against both seasonal and pandemic flu outbreaks. It is likely that new developments in vaccine synthesis and production will be used in the next few years, like the recombinant DNA Flublok vaccine introduced for the 2013-2014 flu season; it is available in both the trivalent and quadrivalent vaccine formulations in 2017 and in the quadrivalent in 2018.

COVID-19 is currently a pandemic disease caused by SARS-CoV-2 virus that has symptoms that can mimic flu symptoms. There is no FDA-approved vaccine against COVID-19, but several vaccines may be approved in a few months in late 2020 to early 2021. The flu vaccine (2020-2021 formulations) will not protect you from COVID-19 because the flu virus and the coronavirus are different viruses. Researchers comment that it is possible to be infected with both the flu virus and coronavirus at the same time. Currently, if you get a flu shot and then get a coronavirus vaccine, it would be safe to do based on experience with previous vaccines. However, since coronavirus vaccines are still being evaluated, there is no data available to confirm this widely held opinion.