This year's epidemic flu season was blamed in part on the challenges in predicting which strains of the influenza virus would be most prominent. Though researchers generally do a good job of predicting which flu strains will be prevelent, the changes in viral make-up make an already difficult job even more so.
The Centers for Disease Control in Atlanta offer the following explanation of how disease strains change over time.
How the Flu Virus Can Change: "Drift" and "Shift"
Influenza viruses can change in two different ways.
One is called "antigenic drift." These are small changes in the virus that happen continually over time. Antigenic drift produces new virus strains that may not be recognized by the body's immune system. This process works as follows: a person infected with a particular flu virus strain develops antibody against that virus. As newer virus strains appear, the antibodies against the older strains no longer recognize the "newer" virus, and reinfection can occur. This is one of the main reasons why people can get the flu more than one time. In most years, one or two of the three virus strains in the influenza vaccine are updated to keep up with the changes in the circulating flu viruses. So, people who want to be protected from flu need to get a flu shot every year.
The other type of change is called "antigenic shift." Antigenic shift is an abrupt, major change in the influenza A viruses, resulting in new hemagglutinin and/or new hemagglutinin and neuraminidase proteins in influenza viruses that infect humans. Shift results in a new influenza A subtype. When shift happens, most people have little or no protection against the new virus. While influenza viruses are changing by antigenic drift all the time, antigenic shift happens only occasionally. Type A viruses undergo both kinds of changes; influenza type B viruses change only by the more gradual process of antigenic drift.