How Flu Viruses Can Change: "Drift" and "Shift"

Antigenic Drift

One way flu viruses change is called "antigenic drift." Drift consists of small changes (or mutations) in the genes of influenza viruses that can lead to changes in the surface proteins of the virus, HA (hemagglutinin) and NA (neuraminidase). The HA and NA surface proteins of influenza viruses are "antigens," which means they are recognized by the immune system and are capable of triggering an immune response, including production of antibodies that can fight infection. The changes associated with antigenic drift happen continually over time as flu viruses replicate (i.e., infect a host and make copies of themselves). Flu vaccines are designed to target one or more of the surface proteins/antigens of flu viruses. For example, egg-based, cell-based, and live attenuated influenza vaccines (nasal spray) flu vaccines all target the HA and NA of the flu viruses they are formulated to protect against. The recombinant flu vaccine only targets the HA of the flu viruses it is formulated to protect against.

The small genetic changes that occur in influenza viruses over time usually produce viruses that are closely related to one another, which can be illustrated by their location close together on a phylogenetic tree. Flu viruses that are closely related to each other usually have similar antigenic properties. This means that antibodies your immune system creates against one flu virus will likely recognize and respond to antigenically similar flu viruses (this is called "cross-protection").

However, the small changes in HA and NA that accumulate over time may result in viruses that are antigenically different, meaning a person's antibodies bind differently or not at all to the virus, resulting in a loss or reduction in protection against that particular flu virus. It also is possible for a single change in a particularly important location on the HA to result in a flu virus becoming antigenically different. When a flu virus has become antigenically different (or "antigenically drifted"), this generally means that the virus' antigenic properties are different enough that the body's immune system (i.e., a person's existing antibodies) will have a harder time recognizing and fighting against the virus. The extent to which a person's immune protection is reduced against an antigenically drifted flu virus can vary, in part because different people may have different levels of pre-existing immunity against that flu virus. Antigenic drift can sometimes result in a person becoming susceptible to flu virus infection again, as antigenic drift has changed the virus' antigenic properties enough that a person's existing antibodies won't effectively recognize and neutralize the antigenically different flu viruses.

Antigenic drift is an important reason why people can get flu multiple times over the course of their lives. Antigenic drift is also a primary reason why the composition of flu vaccines for use in the Northern and Southern Hemispheres is reviewed annually and updated as needed to keep up with evolving flu viruses.

Antigenic Shift

Another type of change is called "antigenic shift." Shift is an abrupt, major change in a flu A virus, resulting in new HA and/or new HA and NA proteins in flu viruses that infect humans. Antigenic shift can result in a new flu A subtype infecting people for the first time. Shift can happen if a flu virus from an animal population gains the ability to infect humans. Such animal-origin viruses can contain HA or HA/NA combinations that are different enough from human viruses that most people do not have immunity to the new (or "novel") virus. Such a "shift" occurred in the spring of 2009, when an H1N1 virus with genes from viruses originating from North American swine, Eurasian swine, humans and birds emerged to infect people and quickly spread, causing a pandemic. When shift happens, most people have little or no immunity against the new virus.

While flu viruses evolve genetically all the time and often undergo antigenic drift, antigenic shift happens infrequently. Flu pandemics occur rarely; there have been four flu pandemics in the past 100 years.