Influenza Vaccination

Although influenza causes significant morbidity and mortality each year, the past two influenza seasons have garnered a lot of media coverage. In addition to the specter of a possible pandemic brewing in South east Asia, the influenza strains contained in the vaccine have not perfectly matched the dominant circulating strains leading some in the public to question the effectiveness of the influenza vaccine. "Why should I get the flu shot when the vaccine doesn't cover the strain that is out there?"

There is an "art" as well as a science to determining the composition of the vaccine from year to year. The process begins with a meeting of World health Organization (WHO) scientists who review the surveillance data form various collection sites from around the world to see what strains of influenza A and B circulated during the last season. From this scientific data they estimate what is likely to be the dominant strain circulating next year. This is not an exact science as a hallmark of influenza viruses is genetic variation. The ultimate result of this variation is the phenomena "antigenic drift" and "antigenic shift". To understand these two concepts one needs to examine the virus and how it can interact the immune system.

Influenza A is an enveloped virus that has two surface proteins hemagglutinin (HA, necessary for attachment to cells) and Neuraminidase (NA, necessary for release of progeny from infected cells). During infection the immune response generates antibodies to these two surface antigens and it is this humoral response that is essential in preventing future infection. Although all of the known subtypes of influenza A (there are currently 15 different HA and 9 different NA subtypes) are found in wild aquatic waterfowl, only two different HA and NA are currently circulating in humans. If an influenza virus that has two completely different HA and NA subtypes are introduced into the population, to which no prior immunity exists the virus can flourish and a pandemic ensues. This is called "antigenic shift". As the virus passes through an immunologically naive group, those that survive infection now have immunity. However because the virus constantly mutates, immunologic pressure forces the virus to change slightly each season. This process called "antigenic drift" is subtler than antigenic shift. Under this immunologic pressure the virus accumulates mutations in the antibody binding regions with in the HA and NA. These changes prevent antibodies generated by previous infection from binding to these antigens, resulting a virus that has "drifted" from its progenitor and now can escape the immune system. It is antigenic drift that makes it necessary to constantly analyze and change the formulation of the vaccine. However, because drift variants are antigenically related the vaccine will provide some protection even in mismatched years and the degree of protection depends on how mismatched the viruses are (ie. how far they have drifted). So what happened in the last two seasons?

Last year the WHO expected that the A/Fujian strain would be the dominant circulating strain. Unfortunately by the time a decision had to be made as to the formulation of the vaccine (a decision that has to be made 6-8 months in advance) there was no isolate that was able to grow well in eggs. Since the influenza vaccine is produced in eggs the only choice was to use the A/ Panama strain that was in the previous years vaccine. So although the dominant strain (A/Fujian) was predicted, its inclusion in the vaccine was hindered by limitations in our current vaccine production process.

Subsequently egg adapted A/Fujian like viruses were available and was included in the 2004-2005 vaccine. During the first half of this season the dominant strain appears to have been A/Fujian, which was included in the 2004-2005 vaccine. During mid season A/California, a drift variant of A/Fujian was identified and is currently circulating across North America. This variant was not identified during the previous influenza season or during this year's season in the Southern Hemisphere. This illustrates the fact that drift variants can unexpectedly arise in the middle of an influenza season and are therefore impossible to predict. There is some data to suggest that the live attenuated vaccine will give better cross protection than the currently available killed vaccine but it too does need to be reformulated yearly. The "holy grail" of influenza vaccinology would be a single vaccine that would be protective against all strains. Although research into this possibility is ongoing, to date this does not exist. Alternatively if we could predict how the virus was going to evolve we could theoretically engineer a vaccine strain, but this too has not come to fruition.

It is important to emphasize that although a drift variant is not a perfect match, it is expected that the vaccine will provide partial protection in immunized individuals who come in contact with the new virus. There is also good evidence that although the influenza vaccine may not prevent infection in these circumstances, it does prevent its complications such as secondary bacterial pneumonia, hospitalizations and death in high-risk individuals and infected individuals often have a milder course. This is particularly true in elderly individuals. Even in years where there is a good match between vaccine and circulating strains, the efficacy of preventing infection is 30-60% but it does prevent complications, hospitalization and death. So despite its apparent flaws, patients should be encouraged to be vaccinated and counseled that the vaccine is safe and beneficial even in mismatched years.

- Todd Hatchette

References:

1. National Advisory Committee Immunization (NACI)'s statement on influenza vaccination for the 2004-2005 season
 
2. Treanor J. Influenza vaccine - outmaneuvering antigenic shift and drift. 2004 NEJM 350:218-220.
 
3. Treanor J. Weathering the vaccine crisis. 2004 NEJM 351: 2037 Ð 2040
 
4. Langley JM, Faughnan ME. Prevention of Influenza in the general population. 2004 CMAJ 171: 1213-1222.