How Are Seasonal Flu Vaccines Made?

Each year, a new flu shot is developed to try to combat the strains of the virus expected to wreak havoc that season. But who decides which viruses make it into the vaccine? What new technologies are being used to produce that vaccine more efficiently?

Sabrina Stierwalt, PhD
5-minute read
Episode #174

Editor's note: This article relates to the seasonal flu vaccine. It is unrelated to the currently ongoing process of developing a COVID-19 vaccine.

You may know that the flu shot changes each year, but how is the vaccine made? Who decides what strains of flu go into the vaccine each year, and how do they make that choice?

What Goes into a Flu Vaccine?

All year long, 142 national influenza centers in 113 different countries collect data on the flu viruses impacting the world’s population. Specifically, they monitor which strains of the virus are making people sick, how efficiently those strains are spreading, and how well previous vaccines have worked to combat their targeted viruses.

All of these smaller centers then pass the results from their wide-reaching investigations to one of five World Health Organization Collaborating Centers for Reference and Research on Influenza: the Centers for Disease Control and Prevention (aka the CDC) in Atlanta, Georgia; the National Institute for Medical Research in London, UK; the Victoria Infectious Diseases Reference Laboratory in Melbourne, Australia; the National Institute for Infectious Diseases in Tokyo, Japan; and the National Institute for Viral Disease Control and Prevention in Beijing, China.

Scientists at each of the five main centers then gather and analyze the data together to identify new flu strains and to determine which strains of the virus are most likely to spread and cause illness in the upcoming flu season. Consultants from each center then meet twice each year. They meet in February to determine the recommended composition for the yearly flu vaccine to be produced in the northern hemisphere for the upcoming flu season, and they also meet in September to make the same decision for future patients in the southern hemisphere.

The virologic surveillance data used to help make their decision are reported through several different channels. Clinical laboratories and hospitals monitor where and when flu cases occur, as well as what strains are detected and what kinds of patients are affected.  Patients who have flu-like symptoms with no other obvious cause but who still do not have officially confirmed cases of the flu are also monitored and recorded. Any changes in the strains of flu themselves, as well as the geographic reach of each strain, are also tracked. To see just how the flu is spreading in your home state, the Epidemiology and Prevention Branch in the Influenza Division at the Centers for Disease Control in the US, produces an interactive report of their findings.

Another factor that can determine which strains of the flu will be included in the current flu shot is the ability to produce a working vaccine against that particular strain. Every vaccine must be thoroughly tested and approved by the FDA before it is made available to the public. If for any reason the production process is particularly slow for a given strain, that strain will not be included in the World Health Organization’s list.

Ultimately, however, the World Health Organization only recommends which viruses go into the flu vaccine each year. Individual countries make the final decision on whether or not to follow that recommendation. In the United States, the US Food and Drug Administration (the FDA) has the final say. To see the make up of the 2015-2016 flu vaccine, check out the CDC’s website.

How are flu vaccines manufactured?

In the US, once the FDA has determined the flu vaccine concoction for the year, all vaccines are then made by manufacturers in the private sector. Private companies can have their own slight variations in the production technologies that they use, but flu shots are most commonly made using fertilized eggs.

A research center, usually the CDC, provides a manufacturer with flu viruses that have been grown in chicken eggs. The manufacturer then injects those viruses into other, fertilized chicken eggs where the are incubated for several days so that the virus can replicate. The fluid containing the virus is then harvested and the virus is killed. (Note that for the nasal spray, an alternative to the flu shot, the virus is merely weakened and not killed entirely.)

Flu shots are most commonly made using fertilized eggs.

The virus antigens—molecular structures found on the surface of the virus’s proteins that are responsible for triggering a body’s immune response, or, in other words, the part of the virus that inspires the production of the antibodies which will eventually fight it off—are then purified. The resulting vaccine is then tested by the FDA on a lot by lot basis before approval.

According to the CDC, the process takes at least six months to produce a vaccine in large quantities. Thus, some manufacturers will make an educated guess as to which strains will need to be harvested for the upcoming flu season and will begin growing some of the virus in January, before the February meeting that produces the recommendations from the World Health Organization so that they are ready to meet demand.

In addition to the long time requirement (relative to the need for yearly updates), the egg-based manufacture of flu vaccines also requires a huge number of eggs. Certain strains of the virus grow poorly in eggs and thus our ability to inoculate against them is limited.

New flu shot technology

Despite having used egg-based production methods for more than 70 years, scientists are now looking to new methods for harvesting the flu virus, in part to produce vaccines more quickly. After being grown in chicken eggs, manufacturers are allowed, since being approved by the FDA in 2012, to harvest the flu virus in canine kidney cells. This process is shorter, and obviously involves fewer eggs, but is currently only being used in one vaccine.

In 2013, the FDA approved the use of recombinant technology, a process that does not use chicken eggs at all. Manufacturers instead harvest proteins directly from the flu virus and combine them with another virus that grows well in insect cells. This combination virus is then allowed to replicate in insect cells before being harvested and purified.

The use of recombinant technology has clear advantages: it does not rely on a supply of virus-containing eggs which come from a limited number of facilities, nor is it limited to the production of vaccines against viruses that can grow well in eggs. Thus, if we face a fast-paced, Contagion-level outbreak of a flu strain, the use of recombinant DNA will allow us to respond quickly.

Who should get a flu shot?

The CDC recommends that anyone over six months of age who is not allergic to the materials used in the production of flu vaccines (like eggs!) should get a flu shot every year, especially those people who spend time around others who are particularly vulnerable to the flu like children and the elderly.

Even if, after all of the extensive data collection and research, the viruses chosen for the flu vaccine are not a good match to those that end up in circulation, the flu shot still offers some protection. Antibodies made by your body in response to the strains of flu in the vaccine can still fight against, although not as effectively, any flu virus that you contract. Every flu shot also contains protection against at least three or four strains, so even if one strain proves to not have its predicted impact, you are still inoculated against the other two or three.

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About the Author

Sabrina Stierwalt, PhD

Dr Sabrina Stierwalt earned a Ph.D. in Astronomy & Astrophysics from Cornell University and is now a Professor of Physics at Occidental College.