Antigenic drift is the accumulation of point mutations in the genes encoding surface antigens, especially the receptor-binding site of hemagglutinin in influenza A. Each mutation slightly reduces the fit of existing antibodies, and over several seasons the accumulated changes are enough that antibodies from an earlier infection no longer neutralize the current strain. Drift is gradual, continuous, and driven by selection on the viral population within hosts that already carry partial immunity. Antigenic shift is a different event entirely: because the influenza genome is segmented, co-infection of one cell by two strains can reassort segments and produce a virus with a hemagglutinin or neuraminidase subtype that has not circulated in humans for decades. The population has little or no pre-existing antibody to that subtype, so shift can seed a pandemic, whereas drift produces seasonal epidemics.
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Immune Evasion Strategies
Drift and Shift: Two Speeds of Antibody Escape
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Watch the two timelines run side by side. On the left, drift: each season a few point mutations appear in the receptor-binding site, and the antibody footprint gradually loses its fit. The change is small per step, but after several seasons the old antibodies no longer neutralize the current strain. On the right, shift: two different strains infect the same cell, their segmented genomes reassort, and a single progeny virus emerges carrying a hemagglutinin subtype the human population has not seen in decades. There is no gradual erosion here, just a sudden reset of pre-existing immunity. That is why drift gives seasonal epidemics and shift can seed a pandemic.
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