The major antigens of the influenza virus, hemagglutinin and neuraminidase, change continuously over time. Subtle changes that occur by spontaneous mutation ("antigenic drift") assure that slightly different viruses circulate each year. As a result, immunity is only partial, even when an individual has been infected or immunized during the previous year.

Occasionally, a novel virus emerges because of a reassortment of the viral RNA segments. Such an event ("antigenic shift") may result in an epidemic influenza season because of the lack of pre-existing immunity in the general population.

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