Abstract
Since the emergence of the ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and the successful rollout of protective vaccines based on this original strain, SARS-CoV-2 has evolved into several variants, in a classical virus-host arms race typical of RNA viruses, to progressively evade the host immune response. Next-generation bivalent vaccines have been developed with broader protection against emerging variants than the ancestral vaccine. Nonetheless, even these vaccines show lower protection against the latest Omicron variants. Immune printing describes how an immune response to an immunogen is impacted by earlier exposures to a related immunogen. Several lessons about the effect of immune imprinting on responses to SARS-CoV-2 infection and vaccination, including age-associated impacts, can be learned from influenza. Understanding the mechanisms of imprinting of SARS-CoV-2 will be important to inform the design of vaccines that produce broader and more durable protective immune responses to emerging variants.