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Influenza A virus (IAV) imposes a significant socioeconomic burden on humanity. Vaccination is effective in only 60% of individuals, even under optimal circumstances. The difficulty stems from the remarkable ability of IAV to evade existing immunity. IAV's error prone polymerase enables the rapid antigenic evolution of the two virion surface glycoproteins, neuraminidase and hemagglutinin (HA). Since the most potent antibodies (Abs) at neutralizing viral infectivity are directed the head of the HA, amino acid substitutions in this region enable IAV to evade Ab-based immunity. Here, we review recent progress in understanding how immunodominance, the tendency of the immune system to respond to foreign immunogens in a hierarchical manner, shapes IAV evolution.

Antibody Immunodominance: The Key to Understanding Influenza Virus Antigenic Drift