How Flu Shots Work—and Why They Sometimes Don't

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Everyone six months and older should get the annual flu shot to help protect against influenza. This is different from many immunizations, which may only require a shot once or twice in a lifetime.

Yearly flu shots are necessary because different flu strains circulate in different flu seasons. You may have had the flu in the past, but your immune system may not yet have confronted the circulating version this year.

This article looks at flu shots, why they're needed, and why they don't always work. It also discusses some of the advances in vaccinations and how you can prevent the spread of influenza.

How the Flu Vaccine Works

When your immune system encounters an invader, it sends white blood cells to counter the threat. Your white blood cells produce antibodies. Antibodies target structures on the surface of the virus called antigens.

When antibodies bind to antigens, they can prevent the virus from being able to enter and infect a cell. They can also alert other white blood cells to come and attack the invader.

This happens naturally when the influenza virus infects you. Unfortunately, the process takes a couple of weeks and can't stop you from getting sick the first time you're exposed to the virus.

The goal of the flu vaccine is to expose your immune system to the virus's antigens before you are infected. That way, your body will have antibodies ready to go when you are exposed to the flu in your community. As a result, you may not get sick at all, or you may only have a milder case.

Verywell / Julie Bang

Viral Mutations

There are different types of flu viruses, including influenza A and influenza B. Each type also has subtypes. In addition, influenza viruses mutate constantly. That's one reason why creating a single flu shot for ongoing protection has been challenging.

When viruses mutate, the antigens change. This means if you have antibodies that worked against a previous strain, they won't work against the new one.

The antigens of the influenza virus are hemagglutinin (HA) and neuraminidase (NA). They are used in naming conventions for influenza, such as H1N1. The flu shot targets the HA antigen, while the nasal spray flu vaccine targets both.

The virus can change in two different ways. A slight change is called a drift, while a major change is called a shift. Interestingly, only influenza A viruses can mutate by shifts. This is what happens when a flu virus that normally infects animals like pigs and birds changes in a way that allows it to infect humans.

When there is a shift, very few people have any immunity to the new strain. These new viruses can have the potential to start a pandemic.

Predictions and Production

The flu vaccine takes at least six months to make. The formula is developed during the previous year's flu season.

Researchers watch circulating strains of influenza closely and try to determine which ones are most likely to make people sick in the coming flu season. The goal is to protect as many people as possible, so the final vaccine usually contains three or four different strains.

Manufacturers begin developing the vaccine up to a month before the new formula is announced. This ensures they'll have time to make enough vaccine.

Typically, one or two of the viruses included in each year's flu shot are updated to anticipate mutations. If a major shift occurs, however, or the virus mutates to a different form than what researchers predicted, the shot may not cover some of the circulating viruses.

If there are circulating viruses that are not covered by the vaccine, you may still get the flu even if you had a flu shot. The good news is that the antibodies your body produces in response to the flu shot typically provide some resistance to mutated versions of that virus.

Even if you do get sick, you are less likely to have a severe case if you have had a flu shot.

Advances in Flu Vaccination

Researchers are working on a universal flu vaccine that will be effective against all strains. This could eliminate the need to develop a new vaccine each year, or even make it so you won't have to get the shot every year. It's an exciting prospect, but the science isn't there yet.

What science has proven is that flu shots are effective. Despite its shortcomings, the vaccine is still the most effective way to prevent infection.

Traditionally, flu vaccines are manufactured by inoculating chicken eggs with the chosen viral strains. After a few days, fluid from the eggs is harvested and purified to make the vaccine.

Both inactivated influenza vaccine and live attenuated influenza vaccine are made this way. An inactivated vaccine uses a killed version of the virus, while a live attenuated vaccine uses a weakened version. The nasal spray flu vaccine is a live attenuated vaccine.

Unfortunately, some influenza viruses, such as the H3N2 viruses, grow poorly in chicken eggs.

In 2012, the FDA approved a process of growing the virus on cell cultures. This results in an egg-free vaccine that may provide better protection than egg-based vaccines in some people. The cell-based technology does not depend on an egg supply and may also allow for faster vaccine production.

A recombinant process was approved in 2013. These vaccines are not made with the flu virus. Instead, they contain synthetically produced antigens. For the 2022-2023 flu season, only one influenza vaccine is built this way in the U.S.

Cell-based and recombinant vaccines represent two significant advances in vaccine technology. There are also developments in vaccines for special populations and circumstances.

Because the immune system's response wanes with age, people aged 65 and over may benefit from different types of flu vaccines. High-dose vaccines contain more antigens than standard flu vaccines, while adjuvant vaccines contain an extra ingredient that helps prompt a more robust immune response. Both these vaccines may provide better protection for older adults.

For the 2022-2023 flu season, the CDC recommended for the first time specific flu vaccines for people 65 years and older:

  • Fluzone High-Dose Quadrivalent (inactivated)
  • Flublok Quadrivalent (recombinant)
  • Fluad Quadrivalent (adjuvanted)

Researchers have also developed an intradermal vaccine that uses less antigen. This technology can help stretch the vaccine supply when necessary. This type of vaccine is injected under the skin rather than into the muscle.

Preventing the Flu

Most healthcare providers recommend getting a flu shot in the fall. However, getting your shot in the winter or spring can still be effective, especially if flu is circulating in your area. It takes about two weeks to get protection from a flu shot.

Good hygiene can also stop the flu from spreading. Wash your hands with soap and water often. If those aren't available, use an alcohol-based hand sanitizer.

For many people, antiviral medication such as Tamiflu (oseltamivir) or Relenza (zanamivir) can help reduce the severity and length of the flu. These medications need to be taken within the first 48 hours of flu symptoms.

These drugs are only available by prescription, so you will have to see your healthcare provider as soon as you develop symptoms. If you have been exposed to someone with the flu, an antiviral medication may also help protect you from getting sick.

Cover your cough to avoid transmitting your sickness to others if you have the flu. Limit your contact with others and stay home if you are sick. You should remain at home at least until your fever has been gone for 24 hours without using fever-reducing medicine.


The flu shot is the best way to protect yourself and your community from influenza. It may not work as well in some years as others, however. This is because flu viruses are always changing, and vaccine developers have to try to accurately predict which ones are most likely to make people sick.

Even if this year's vaccine doesn't keep you from getting sick, it can still help prevent a severe case of the flu. Taking an antiviral medication in the first 48 hours can also keep you from getting very sick.

Frequent hand washing can help stop the flu from spreading. If you are sick, stay home until 24 hours after your fever goes away.

A Word From Verywell

According to the CDC, the only people who should not get the flu vaccine are those younger than six months of age and those allergic to the flu vaccine or its ingredients.

Take every step you can to protect yourself, your family, and your community from the flu. It's not a mild or minor disease. In the 2017 to 2018 flu season, for example, 41 million Americans were sickened and 52,000 died of influenza. You have the ability to reduce the risk.

12 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Kristina Duda, RN
Kristina Duda, BSN, RN, CPN, has been working in healthcare since 2002. She specializes in pediatrics and disease and infection prevention.