How the Flu Vaccine Is Made and Why It Changes Every Year
The flu vaccine changes yearly because flu viruses mutate and protection fades. How strains are picked and how egg, cell and recombinant shots are made.
The flu vaccine is made from the specific influenza strains that scientists expect to circulate in the coming season, and it changes every year because flu viruses mutate constantly and the body’s protection from a flu shot fades over the following months. Health agencies pick the strains about six months before flu season starts, and manufacturers then grow the virus or its surface protein in chicken eggs, in animal cell cultures or with recombinant technology.
Why does the flu vaccine change every year?
Influenza viruses change their surface proteins through small, steady mutations, a process called antigenic drift. The immune system recognizes flu mainly by two proteins on the outside of the virus: hemagglutinin (the H in names like H1N1) and neuraminidase (the N). When enough small changes pile up in these proteins, antibodies made against last year’s version no longer bind well, and the vaccine has to be updated to match.
Occasionally a much bigger change happens. Antigenic shift occurs when a flu virus picks up an entirely new hemagglutinin, sometimes by swapping genes with a flu virus from birds or pigs. Most people have little or no immunity to such a virus, and shifts of this kind caused the flu pandemics of 1957, 1968 and 2009.
A second reason for a yearly shot is that immunity from the vaccine itself wanes. Antibody levels fall over several months, so even when the strains stay the same, the US Centers for Disease Control and Prevention recommends a new dose each season for nearly everyone 6 months and older.
Who decides which strains go into the vaccine?
The World Health Organization runs a worldwide surveillance network that collects and tests flu samples all year. National influenza centers in many countries send viruses to WHO collaborating centers, which compare them with existing vaccine strains and track which ones are spreading.
WHO advisers meet twice a year to recommend strains: in February for the Northern Hemisphere and in September for the Southern Hemisphere. In the United States, an advisory committee to the Food and Drug Administration reviews the data and makes the final choice for US vaccines, usually in early spring.
Most US flu vaccines now protect against three strains:
- an influenza A(H1N1) virus
- an influenza A(H3N2) virus
- an influenza B virus from the Victoria lineage
For years many vaccines also included a fourth strain from the B/Yamagata lineage. That lineage has not been detected in global surveillance since 2020, so US vaccines switched back to a three-strain formula starting with the 2024-2025 season.
How are flu vaccines made in eggs?
Egg-based production is the oldest method and still makes most flu vaccine in the US. Labs first create a “candidate vaccine virus” for each chosen strain, often a hybrid that carries the new strain’s surface proteins and grows well in eggs.
- Each candidate virus is injected into fertilized chicken eggs.
- The eggs are incubated for several days while the virus multiplies in the fluid around the embryo.
- The fluid is harvested and the virus is purified.
- For flu shots, the virus is inactivated (killed) and usually split apart, so the shot contains viral proteins that cannot cause infection.
- Each strain is tested for strength and purity, then the strains are blended, filled into vials and syringes, and checked again before release.
The whole process takes about six months, which is why strain selection happens so early. It also needs a very large supply of eggs. The nasal spray vaccine, used for some healthy people aged 2 through 49, is also grown in eggs, but it contains a live virus weakened so that it replicates only in the cooler nose and not in the lungs.
What are cell-based and recombinant flu vaccines?
Cell-based vaccines grow the virus in cultured mammalian cells instead of eggs. The FDA approved the first one in the US in 2012. Cell culture does not depend on egg supplies, and it avoids a known problem: flu viruses grown in eggs can pick up small changes that help them grow there, which can make the vaccine a slightly weaker match for the virus spreading in people.
Recombinant vaccines skip growing flu virus altogether. Scientists take the gene for the hemagglutinin protein, insert it into another virus that infects insect cells, and let those cells produce large amounts of the flu protein. The protein is then purified and made into a vaccine. Because it does not need a live flu sample, this method can move faster once a strain is chosen.
All three methods produce vaccines that target the same recommended strains, and all go through the same FDA review for each season’s formula.
Why is the flu vaccine sometimes a poor match?
The strain choice is a forecast made months in advance. If a different version of a virus becomes dominant after production starts, the vaccine may match it less well. H3N2 viruses drift faster than the others and are the most common source of mismatch. Egg-adapted changes, described above, can widen the gap for H3N2 in particular.
According to the CDC, flu vaccination reduces the risk of a doctor’s visit for flu by roughly 40% to 60% in seasons when the vaccine is well matched to circulating viruses. Protection is lower in poorly matched seasons, but vaccination still tends to reduce the risk of severe illness and hospitalization.
Can the flu shot give you the flu?
A flu shot cannot give you the flu, because injected vaccines contain either inactivated virus or a single viral protein, and neither can cause an infection. Soreness at the injection site, mild fever or aches for a day or two are common side effects and come from the immune response. It takes about two weeks after vaccination for protection to build, so a person exposed to flu in that window can still get sick.
Flu spreads most in the colder months, and the reasons are covered in our article on why colds and flu peak in winter. In the US, flu activity usually starts rising in October and peaks between December and February, the same stretch when cold-air events such as a weakening polar vortex make the weather news.
Quick answers
When is the best time to get a flu shot?
The CDC advises that most adults get vaccinated in September or October, before flu starts spreading widely. Getting vaccinated later in the season still provides protection.
Is the Southern Hemisphere flu vaccine different?
Yes. WHO picks its strains in September, about six months after the Northern Hemisphere choice, so it can include newer versions of the viruses.
Will there ever be a universal flu vaccine?
Researchers are working on vaccines that target parts of the flu virus that change little from year to year. None is approved yet, so annual vaccination remains the standard recommendation.
Are people with egg allergies able to get a flu vaccine?
The CDC says people with egg allergies can receive any flu vaccine appropriate for their age and health, and egg-free cell-based and recombinant options also exist.
