Selecting the Viruses in the Seasonal Influenza (Flu) Vaccine

Questions & Answers

What kind of flu vaccines are there?

There are two influenza (flu) vaccines. The “flu shot” is an inactivated vaccine (containing killed virus) given with a needle and injected into the muscle. There also is a nasal-spray flu vaccine (sometimes called LAIV for Live Attenuated Influenza Vaccine) that contains weakened live viruses. It takes about two weeks after vaccination to develop antibodies to protect against infection by viruses similar to those in the vaccine.

What does the seasonal influenza vaccine protect against?

Each year, the seasonal influenza vaccine contains three influenza viruses — one influenza A (H3N2) virus, one seasonal influenza A (H1N1) virus, and one influenza B virus. The influenza viruses in the seasonal flu vaccine are selected each year based on surveillance-based forecasts about what viruses are most likely to cause illness in the coming season. Therefore, each year’s seasonal flu vaccine is designed to protect against the influenza viruses expected to cause disease during the upcoming influenza season.

In April 2009, a new and different virus called 2009 H1N1 Influenza caused widespread illness and resulted in the first influenza pandemic in 40 years. It is likely that the 2009 H1N1 influenza virus will continue to circulate and cause illness during the 2010-2011 flu season. The 2010-2011 flu vaccine will protect against the 2009 H1N1 virus, as well as two other influenza viruses: an influenza A H3N2 virus, and an influenza B virus.

How are the viruses selected to make flu vaccine?

The influenza (flu) viruses selected for inclusion in the seasonal flu vaccines are updated each year based on which influenza virus strains are circulating, how they are spreading, and how well current vaccine strains protect against newly identified strains. Currently, 130 national influenza centers in 101 countries conduct year-round surveillance for influenza and study influenza disease trends. These laboratories also send influenza viruses to the five World Health Organization (WHO) Collaborating Centers for Reference and Research on Influenza located in Atlanta, Georgia, USA (Centers for Disease Control and Prevention, CDC); London, United Kingdom (National Institute for Medical Research); Melbourne, Australia (Victoria Infectious Diseases Reference Laboratory); Tokyo, Japan (National Institute for Infectious Diseases); and Beijing, China (National Institute for Viral Disease Control and Prevention) for additional analyses.

The seasonal flu vaccine is a trivalent vaccine (a three component vaccine) with each component selected to protect against one of the three main groups of influenza viruses circulating in humans. (Last year's 2009 H1N1 vaccine was made in response to the pandemic first recognized in April 2009. Unlike seasonal flu vaccines, the pandemic vaccine protected against only one flu virus strain, the 2009 H1N1 virus.)

The influenza viruses in the seasonal flu vaccine are selected each year based on surveillance-based forecasts about what viruses are most likely to cause illness in the coming season. WHO recommends specific vaccine viruses for inclusion in influenza vaccines, but then each individual country makes their own decision for which strains should be included in influenza vaccines licensed in their country. In the United States, the U.S. Food and Drug Administration (FDA) determines which vaccine viruses will be used in U.S.—licensed vaccines.

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What other factors can influence which viruses are chosen to go into the seasonal flu vaccine?

Another important practical factor in the recommendation about what viruses should be included in a flu vaccine is whether or not there is a good vaccine virus strain available that would likely provide good protection against viruses likely to circulate in the upcoming year. A vaccine virus is one that can be used to make vaccine. Vaccine viruses must be similar to other influenza viruses that are forecast as being the most likely to circulate during the upcoming year and must be grown from a clinical specimen in eggs or special pathogen free chicken kidney cells, but not in any other cell lines. Vaccine virus strains must be tested and available in time to allow for production of the large amount of vaccine virus needed to make the vaccine. Occasionally, a suitable new vaccine virus cannot be identified in time for inclusion in the upcoming year’s vaccine.

How is all of this information used?

Twice a year, the World Health Organization (WHO) organizes a consultation with the Directors of the WHO Collaborating Centers and representatives of key national laboratories. They review the results of surveillance, laboratory and clinical studies, and the availability of vaccine virus strains and make recommendations on the composition of the influenza vaccine. These meetings take place in February for making recommendations about the composition of the vaccine for the upcoming Northern Hemisphere’s seasonal influenza vaccine and in September for the Southern Hemisphere’s vaccine. WHO recommends specific vaccine viruses for inclusion in influenza vaccines, but then each individual country makes their own decision for which strains should be included in influenza vaccines licensed in their country. In the U.S., the Food and Drug Administration (FDA) makes the final decision about vaccine strains for influenza vaccines to be sold in the U.S. Information about circulation of influenza viruses and identified vaccine virus strains is summarized and presented to an advisory committee of the FDA in February each year for the U.S. decision about which virus strains to include in the upcoming year’s vaccine.

What is CDC’s Influenza Division’s role in vaccine 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 yearly seasonal vaccine virus selection process for the Southern and Northern Hemispheres. CDC plays a major role in testing and identifying new variants of influenza viruses and identifying vaccine virus strains through their global surveillance activities. The Influenza Division provides this information to other directors of WHO Collaborating Centers and representatives of key national laboratories and participates in discussions regarding which strains will be recommended for inclusion in the flu vaccine. CDC also presents information to FDA’s advisory committee for their decision making and helps to identify vaccine viruses.

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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 virus strains for the vaccine even before a WHO or FDA decision is made based on what they think may be the recommended strains. 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 October and November, manufacturers may begin to grow one or more of the virus strains in January based on their best guess as to what strains are most likely to be included in the vaccine.

What determines the effectiveness of the seasonal influenza vaccine each year?

How well the flu vaccine works each year depends in part on how closely related (or “matched”) the viruses in the vaccine are to the flu viruses circulating that year. Vaccine effectiveness also varies depending on how well a vaccinated person responds to the vaccine in terms of making protective antibody, and how successful vaccination programs are at vaccinating people in advance of the season. Elderly persons and others who may have weakened immune systems may have a lower antibody response than young, healthy persons. However, elderly and other persons with weakened immune systems still benefit from vaccination. For more information see Vaccine Effectiveness - How Well Does the Flu Vaccine Work?

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What is meant by a “good match” between viruses in the vaccine and circulating influenza viruses?

A good match is said to occur when the viruses in the vaccine and the viruses circulating among people during a given influenza season are closely related and the antibodies produced by the vaccine are able to provide protection against infection.

What if there is a mismatch between circulating viruses and the vaccine viruses?

A “mismatch” is said to occur when the viruses in the vaccine are significantly different from those circulating in the community. In years when the vaccine strains are not well matched to circulating strains, vaccine effectiveness can be reduced. However, even when the viruses in the vaccine and circulating viruses are not well matched, a vaccine may still offer some protection against circulating viruses.

For example, in a study among persons 50-64 years of age during the 2003-04 influenza season, when the vaccine strains were not optimally matched, inactivated influenza vaccine effectiveness against laboratory-confirmed influenza was 60% among persons without high-risk conditions, and 48% among those with high risk conditions. However, vaccine effectiveness was 90% against laboratory-confirmed influenza hospitalization (Herrera, et al Vaccine 2006). A study in children during the same year found vaccine effectiveness of about 50% against medically diagnosed influenza and pneumonia without laboratory confirmation (Ritzwoller, Pediatrics 2005). Still, in some years when vaccine and circulating strains were not well-matched, no vaccine effectiveness may be able to be demonstrated (Bridges, JAMA 2000). It is not possible in advance of the influenza season to predict how well the vaccine and circulating strains will be matched, and how that may affect vaccine effectiveness. For more information, see Vaccine Effectiveness - How Well Does the Flu Vaccine Work?

How do we know if the vaccine is a good match?

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. CDC also conducts studies to determine the effectiveness of the seasonal vaccine against circulating viruses. For more information about CDC’s surveillance and to access the weekly reports, visit Flu Activity and Surveillance.

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Can the seasonal flu vaccine provide protection even if the vaccine is not a “good” match?

Yes, antibodies created through vaccination with one strain of influenza viruses will often offer protection against related strains of influenza viruses. So even though circulating influenza viruses may “drift” or change from the time the vaccine composition is recommended, the vaccine may cross-protect against circulating viruses. The mismatch may result in reduced effectiveness against the variant viruses, but it still can provide some protection. In addition, it’s important to remember that the influenza vaccine contains three virus strains; so the vaccine would still protect against the other two viruses. For these reasons, even during seasons when there is a mismatch, CDC continues to recommend seasonal influenza vaccination. This is particularly important in people at high risk for serious flu-related complications and for close contacts of high risk people.

Why is it sometimes difficult to get a good vaccine virus strain for vaccine production?

There are a number of factors that can make getting a good vaccine virus strain for vaccine production challenging, including both scientific issues and issues of timing. Currently, only viruses grown in eggs can be used as vaccine virus strains. If specimens have been grown in other cell lines, they cannot be used for vaccine strains. However, more and more laboratories do not use eggs to grow influenza viruses, making it difficult to obtain potential vaccine strains. In addition, some influenza viruses, like H3N2 viruses, grow poorly in eggs, making it even more difficult to obtain possible vaccine strains.

In terms of timing, in some years certain influenza viruses may not circulate until later in the influenza season, or a virus can change late in the season or from one season to the next. This can make it difficult to forecast which viruses will predominate the following season, but it can also make it difficult to identify a vaccine virus strain in time for the production process to begin. WHO Collaborating Centers need to evaluate many viruses from each type or subtype to be able to determine if and how the viruses are changing and which virus would make the best vaccine virus strains. In some years, too few viruses of a particular type or subtype are available to make this determination by the time a decision must be made about vaccine strain selection.

Besides vaccination, what can I do to protect myself against influenza?

The best way to prevent the flu is to get vaccinated, but antiviral medications are an important second line of defense that can be used to treatment flu and may also be used for prevention. These medications must be prescribed by a doctor. Visit What You Should Know About Flu Antiviral Drugs for more information about antiviral drugs. There also are certain “good health habits” that may help reduce the spread of respiratory illnesses like the flu, including covering your cough and washing your hands often. For more information on this topic, visit Good Health Habits.

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