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. About two weeks after vaccination, antibodies develop in the body that 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 a?? one influenza A (H3N2) virus, one regular seasonal influenza A (H1N1) virus (not the 2009 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 yeara??s seasonal flu vaccine is designed to protect against the seasonal influenza viruses expected to cause disease during that influenza season.

This year there is a new and very different flu virus spreading worldwide among people called 2009 H1N1 flu. The seasonal flu vaccine is unlikely to provide protection against 2009 H1N1 influenza. This year, there also is a 2009 H1N1 vaccine currently in production The 2009 H1N1 vaccine is not intended to replace the seasonal flu vaccine a?? it is intended to be used along-side seasonal flu vaccine.

How are viruses chosen for the seasonal flu vaccine each year?

The viruses used in making seasonal flu vaccine are chosen each year based on information gathered over the previous year about the strains of flu viruses that are infecting humans and how they are changing. Circulating influenza strains and information on disease trends are gathered by 122 national influenza centers in 94 countries and the viruses and other data are further tested and combined data are analyzed by the four World Health Organization (WHO) Collaborating Centers for Reference and Research on Influenza located at the Centers for Disease Control and Prevention (CDC) in Atlanta; London, United Kingdom; Melbourne, Australia; and Tokyo, Japan. Based on this information, experts forecast which viruses are likely to circulate the following season and WHO recommends specific virus strains that can be used to make vaccines to protect against them. For vaccines being made for the Northern Hemisphere, the recommendation is made by WHO in February each year. For vaccines being made for the Southern Hemisphere, the recommendation is made by WHO in September. Each country then can use the recommendations made by WHO to assist with national decisions about what viruses to use in influenza vaccines for their country. In the U.S., an advisory committee convened by the Food and Drug Administration (FDA) makes the final decision about vaccine strains in February. Manufacturers grow vaccine strains based on these recommendations; but they often begin the production process as early as January based on their assessment of which strains will be chosen for the vaccine.

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 reference vaccine virus available from all the viruses collected and analyzed by the WHO Collaborating Centers that would likely provide good protection against viruses likely to circulate in the upcoming year. A reference vaccine virus is one that can be used to make vaccine. Reference 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. Reference strains must be identified in time to allow for production of the large amount of vaccine virus needed to make the vaccine. Occasionally, a suitable new reference vaccine virus cannot be identified in time for inclusion in the upcoming yeara??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 reference vaccine strains and make recommendations on the composition of the influenza vaccine. These meetings take place in February for the Northern Hemisphere and in September for the Southern Hemisphere. The three virus strains that WHO recommends for the influenza vaccine are selected at these meetings. Each country then makes their own decision about what viruses to use in influenza vaccines for 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 reference vaccine strains is summarized and presented to an advisory committee of the FDA in February each year for the U.S. decision about what virus strains to include in the upcoming yeara??s vaccine.

What is CDC’s Influenza Division’s role in vaccine selection?

As one of four WHO Collaborating Centers, CDCa??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 reference vaccine 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 FDAa??s advisory committee for their decision making and helps to identify reference vaccine viruses.

What happens after a recommendation has been made about what 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 (prior to the start of the flu season), manufactures 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 on how closely related (or a??matcheda??) 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 How Well Does the Seasonal Flu Vaccine Work? Seasonal Influenza Vaccine Effectiveness.

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.

Past studies have shown that in years when the vaccine viruses and circulating viruses are well-matched, the vaccine can reduce the chances of getting the influenza by 70%-90% in healthy adults. The vaccine may be somewhat less effective in elderly persons and very young children, but vaccination can still prevent serious complications from the flu. In healthy adults younger than 65 years of age, the flu vaccine can also prevent lost work days, and lessen the number of doctor visits made and the number of courses of antibiotics used.

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

A a??mismatcha?? is said to occur when the viruses in the vaccine are significantly different from those circulating in the community. 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.

In years when the vaccine strains are not well matched to circulating strains, vaccine effectiveness can be reduced. For example, in a study among persons 50-64 years of age during the 2003-04 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, but it 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). However, 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 How Well Does the Seasonal Flu Vaccine Work? Seasonal Influenza Vaccine Effectiveness.

Can the seasonal flu vaccine provide protection even if the vaccine is not a a??gooda?? 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 a??drifta?? or change from the time the vaccine composition is recommended, the vaccine can cross-protect against circulating viruses. The mismatch may result in reduced effectiveness against the variant viruses, but it still can provide enough protection to lessen illness severity. In addition, ita??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.

It is important to note that this year there is a new and very different flu virus spreading worldwide among people called 2009 H1N1 flu. The seasonal flu vaccine is unlikely to provide protection against 2009 H1N1 influenza because the new H1N1 virus is very different from the seasonal H1N1 virus in the seasonal flu vaccine. However a 2009 H1N1 vaccine is currently in production. The 2009 H1N1 vaccine is not intended to replace the seasonal flu vaccine a?? it is intended to be used along-side seasonal flu vaccine.

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

There are a number of factors that can make getting a good reference vaccine strain for vaccine production challenging, including both scientific issues and issues of timing. Currently, only viruses grown in eggs can be used as reference vaccine strains. If specimens have been grown in the cell lines that are most often used to grow influenza viruses, they cannot be used for vaccine strains. Today 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 what virus will predominate the following season, but it can also make it difficult to identify a reference vaccine 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 reference vaccine 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 in the prevention and treatment of flu. These medications must be prescribed by a doctor. Visit Treatment and Prevention: Influenza Antiviral Drugs for more information about antiviral drugs. There also are certain a??good health habitsa?? that may help prevent the spread of respiratory illnesses like the flu: including covering your cough and washing your hands often. For more information about on this topic, visit Good Health Habits for Preventing Seasonal Flu.

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

CDCa??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 CDCa??s surveillance and to access the weekly reports, visit Flu Activity & Surveillance.