Influenza Virus Antigenic Drift: Balancing Fitness and Immune Evasion

Human influenza viruses demonstrate immense antigenic variability as a strategy to evade host immunity. The process of evolving to evade host antibody responses, known as antigenic drift, allows influenza viruses to evade epitope-specific antibodies, leading to seasonal influenza outbreaks. Neutralizing antibodies, the major drivers of antigenic drift, target a wide range of epitopes in hemagglutinin and neuraminidase, including functionally conserved regions. In this review, we describe antibody targets of influenza viruses, how influenza viruses have evolved to evade these antibody specificities, and how epistasis helps maintain viral fitness. Then we discuss emerging approaches to study and predict antigenic drift that may improve strain selection for seasonal influenza vaccines.