Harnessing immune history to combat influenza viruses

Individuals are exposed to influenza viruses throughout their lifetime. Accumulating evidence shows the first viruses an individual is exposed to leaves an imprint on the antibody response induced by subsequent drifted and novel influenza viral exposures. Imprinted humoral immunity against influenza viruses relies on biased immune memory to influenza viruses for which memory B cell responses were initially generated against. Imprinting allows for antibodies to adapt to drifted influenza viruses while maintaining binding potential for the first influenza viruses an individual is exposed to. However, imprinting can increase susceptibility to non-imprinted influenza viruses and mismatched influenza viruses. This review highlights the role of imprinting on the regulation of antibody responses induced by influenza viruses and explores potential vaccine strategies to harness imprinted antibody responses to increase protection against influenza.