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Part 3: Why do we get the flu again and again?

And why can't we develop a one-time flu vaccine?

To best understand the material in this web article, read the sections in our textbook that explain how the immune system works. (Dragonfly book Sections 40-1 and 40-2; Elephant book sections 45-1 and 45-2.)

Researchers have been able to devise vaccines that offer powerful and long-lasting protection against many viruses cause serious diseases in humans. (See Dragonfly pages 1041 - 1042). When you were very young, for example, you were probably vaccinated against measles and several other diseases. When your parents or grandparents were young, they were probably vaccinated against polio, which was still common as recently as the 1950ıs. And when the authors of your text were young, we were also vaccinated against smallpox before leaving the United States.

Now that we bring this subject up, you might wonder why flu shots offer protection for only one season at a time — if they work at all. The answer can be found in the way our immune system operates, the speed at which these viruses evolve, and the host species that they infect.

The key to understanding this situation is appreciating the way our immune system identifies and attacks foreign invaders (Dragonfly book section 40-2; Elephant book section 45-2). Remember that our the immune system doesn't actually recognize an entire virus. Instead, various immuneT-cells and B-cells "learn" to identify and remember only certain particular proteins on the outside of the viral coat. If the coat proteins f a virus never change, an immune system exposed to that virus once can "remember" it for a long time, and rapidly mount an attack against it.

That is the situation with smallpox. The smallpox virus is a genetic stick-in-the-mud. Its genes, and therefore its coat proteins, don't change much over time. For that reason, the coat proteins of a smallpox virus collected in 1950 will probably closely resemble the coat of another sample collected in 1960, 1970 or even 2000. What's more, the smallpox virus infects only a single host species: Homo sapiens.

For these reasons, the World health organization was able to mount a worldwide smallpox vaccination program that eliminated the disease by 1980. How was that possible? Because the smallpox virus doesnıt evolve rapidly, so a single dose of smallpox vaccine protects against infection for years. When as enough humans around the world were vaccinated, the smallpox virus could not "find" vulnerable hosts, and therefore couldn't survive and reproduce in human populations. And because smallpox doesn't have any animal hosts, once humans were immune, the virus had nowhere to grow at all. Until the threat of bioterrorism emerged, this virus was effectively out of business. (That's why almost no one under the age of 30 in this country has been vaccinated against smallpox — which unfortunately makes this virus attractive as a weapon for terrorists.)

The situation with influenza, on the other hand, is different for two reasons.

1. Influenza viruses evolve rapidly.   

Flu viruses mutate and evolve rapidly. (In fact, it has been estimated that the proteins of the influenza virus evolve as much as a million times faster than most human proteins!) For this reason,  so new and slightly different viral strains appear all the time. The differences among these new strains often include changes in coat proteins. Therefore, any immune system memory cells produced by a vaccination or previous infection no longer recognize the new strains. When that happens, the immune response must mount a defense from scratch, and the viruses have enough time to make the host sick.

If you think about this, you can probably see how our immune response creates a form of natural selection that drives the evolution of these viruses. Here's why. Strains that don't change their coat protein are stopped by the immune response before they can spread. These strains, therefore, have substantially lowered fitness, and are effectively wiped out. Strains that change their coat proteins, on the other hand, have higher fitness. These strains delay the immune response long enough to make us sick — which forces us to spread the virus to new hosts by coughing and sneezing.

In this highly simplified schematic diagram, a human antibody formed form a previous exposure to a viral strain matches a particular coat protein (the antigen). This kind of match spurs the immune system into immediate action that prevents the virus from causing seirous illness.

In this schematic, that same antibody encounters a new viral antigen — which it does not recognize. If none of the body's circulating antibodies recognize this new strain, it will take time for the immune system to identify and fight the invader.

As a result of these selective pressures, the flu strains that appear and spread successfully each year are different enough from last year's strains to evade memory cells left over from previous infections. Even during a single flu season, new strains can emerge with coat proteins that are slightly different from the first strains in circulation. That explains both why you can even catch the flu several times in a single season. The determining factor is whether or not the strains you are exposed to are different enough from each other to confuse your immune system.

2. Influenza viruses infect a wide variety of domestic and wild animal species.

In addition to this constant evolutionary "cat and mouse" game with human immune systems, several strains of influenza virus can survive and reproduce in other animal hosts. For that reason, even if all humans in a given area acquire resistance to the virus, those strains can survive in other species long enough to mutate and infect humans again later on.


Childhood vaccinations against a variety of bacterial and viral diseases are not only recommended, but required by most public school systems in the US today.

This young African man was identified two decades ago by the WHO as the last known, naturally occurring smallpox patient



Index of this Web Article:

• Introduction — What's up with the Flu?
• What is influenza — and who gets it?
Why can we get the flu again and again? And why can't we develop a one-time flu vaccine?
• How are flu vaccines made?
• Why are flu vaccines sometimes not effective?
• Why are researchers so worried about this new bird flu?

Other Sections