Selecting Viruses for the Seasonal Influenza Vaccine
The seasonal influenza (flu) vaccine is designed to protect against the three or four influenza viruses that research indicates are most likely to spread and cause illness among people during the upcoming flu season. Flu viruses are constantly changing, so the vaccine composition is reviewed each year and updated as needed based on which influenza viruses are making people sick, the extent to which those viruses are spreading, and how well the previous season’s vaccine protects against those viruses.
More than 100 national influenza centers in over 100 countries conduct year-round surveillance for influenza. This involves receiving and testing thousands of influenza virus samples from patients. The laboratories send representative viruses to five World Health Organization (WHO) Collaborating Centers for Reference and Research on Influenza, which are located in the following places:
- Atlanta, Georgia, USA (Centers for Disease Control and Prevention, CDC)
- London, United Kingdom (The Francis Crick Institute)
- Melbourne, Australia (Victoria Infectious Diseases Reference Laboratory)
- Tokyo, Japan (National Institute for Infectious Diseases)
- Beijing, China (National Institute for Viral Disease Control and Prevention)
Twice a year, the World Health Organization (WHO) organizes a consultation with the Directors of the six WHO Collaborating Centers, Essential Regulatory Laboratories and representatives of key national laboratories and academies. They review the results of surveillance, laboratory, and clinical studies, and the availability of vaccine viruses and make recommendations on the composition of the influenza vaccine. These meetings take place in February for selection of the upcoming Northern Hemisphere’s seasonal influenza vaccine and in September for the Southern Hemisphere’s vaccine. The WHO recommends specific vaccine viruses for inclusion in influenza vaccines, but then each country makes their own decision about which viruses should be included in influenza vaccines licensed in their country.
In the United States, the Food and Drug Administration (FDA) makes the final decision about vaccine viruses for domestic influenza vaccines. Information about the circulation of influenza viruses and available vaccine viruses is summarized and presented to an advisory committee of the FDA in February each year for the U.S. decision about which viruses to include in the upcoming season’s vaccine.
What are the main factors that influence which viruses are selected for use in vaccine production?
The influenza viruses in the seasonal flu vaccine are selected each year based on surveillance data indicating which viruses are circulating and forecasts about which viruses are the most likely to circulate during the coming season. The degree of similarity between available vaccine viruses and circulating viruses also is important. Vaccine viruses must be similar to the influenza viruses predicted to circulate most commonly during the upcoming season. Another important factor is whether or not there is a good vaccine virus available; that is, a virus that could be used in vaccine production and which would likely protect against the viruses likely to circulate during the upcoming season. Historically, vaccine viruses were required by FDA to be isolated and grown in chicken eggs, but now the FDA allows vaccine viruses to be grown in cells, too. Regardless of how they are grown, vaccine viruses must be tested and available in time to allow for manufacturers to produce the large amount of vaccine virus needed to make vaccine.
Why is it sometimes difficult to get a good vaccine virus for vaccine production?
There are a number of factors that can make getting a good vaccine virus for vaccine production challenging, including both scientific issues and issues of timing. FDA regulatory requirements now allow influenza vaccine viruses to be grown in chicken eggs or cells. Today, the majority influenza vaccines are still grown in chicken eggs. Some influenza viruses, like H3N2 viruses, grow poorly in eggs, making it challenging to obtain good candidate vaccine viruses at times.
In some years certain influenza viruses may not appear and spread until later in the influenza season, making it difficult to prepare a candidate vaccine virus in time for vaccine production. This can make vaccine virus selection very challenging.
What is CDC’s Influenza Division’s role in vaccine virus selection?
As one of five WHO Collaborating Centers, CDC’s Influenza Division receives and tests thousands of influenza viruses from around the world each year and collaborates with other WHO Collaborating Centers and National Influenza Centers in the bi-annual seasonal vaccine virus selection process for the Southern and Northern Hemispheres. CDC plays a major role in testing and identifying new strains of influenza viruses through their global surveillance activities and then preparing candidate vaccine viruses. The Influenza Division provides this information to the directors of other WHO Collaborating Centers, essential regulatory laboratories and representatives of key national laboratories and academies and then participates in discussions regarding which viruses will be recommended for inclusion in flu vaccines. CDC also presents information to FDA’s advisory committee for their decision making and helps to identify vaccine viruses.
CDC’s Influenza Division collects and reports information on influenza activity in the United States each week. Laboratory studies of circulating influenza viruses allow CDC to evaluate how close a match there is between viruses in the vaccine and circulating viruses each season. Antigenic characterization is one process that can give an indication of the flu vaccine’s ability to produce an immune response against the influenza viruses circulating in people. Genetic characterization also can inform decision-making for vaccine virus selection. CDC also conducts studies to determine the effectiveness of the seasonal vaccine against circulating viruses. For more information, see Vaccine Effectiveness – How Well Does the Flu Vaccine Work? For more information about CDC’s surveillance and to access the weekly reports, visit Flu Activity and Surveillance.
What happens after a recommendation has been made about which viruses should be included in the seasonal flu vaccine?
As soon as a recommendation has been issued about what viruses should be included in the vaccine, private sector manufacturers begin the process of producing vaccine. In fact, some manufacturers may start growing one or more viruses for the vaccine even before a WHO or FDA decision is made based on what they think may be the recommended vaccine viruses. This allows manufacturers more time to make vaccine for the fall; the more time a manufacturer has to make vaccine, the greater the number of doses that can be produced.
How long does it take to manufacture seasonal influenza vaccine?
It takes at least six months to produce large quantities of influenza vaccine. For vaccine to be delivered in time for vaccination to begin in the fall, manufacturers may begin to grow one or more of the vaccine viruses in January based on their best guess as to what viruses are most likely to be included in the vaccine. For information about flu vaccine production, see How Influenza (Flu) Vaccines Are Made.