The immune responses elicited by subpotent vaccines may exert selection pressure that favors antigenic drift and shift ( Figure) . Antigenic drift relies on the accumulation of mutations within the antibody-binding sites in the hemagglutinin (HA), neuraminidase (NA), or both that abrogate the binding of antibodies. This makes infl uenza A virus strains able to evade neutralizing antibody from prior infection or vaccination. Antigenic shift, which is seen only with infl uenza A viruses, is a more drastic change. It results from genetic shift by reassortment exchange of the HA, and sometimes the NA, with novel subtypes that have not been present in human viruses for a long time. Antigenic shift leads to replacement of circulating strains with new variants that are able to reinfect hosts immune to earlier types; the result is usually a pandemic. Antigenic shifts caused 2 of the major infl uenza A pandemics in the last century, including the 1957 subtype H2N2 and 1968 subtype H3N2 outbreaks (10) .