Influenza vaccines delivered in early childhood could turn antigenic sin into antigenic blessings

Substantial evidence has accumulated that “original antigenic sin” is a central factor shaping immune responses against influenza viruses. Here, we argue that this propensity of initial influenza virus exposure to establish a lifelong immunological imprint presents a remarkable opportunity: Immunization of infants prior to their initial, natural viral exposure could circumvent narrow immunological imprinting directed toward a single viral strain. Simultaneous initial exposure to antigens from multiple influenza strains via vaccination holds the promise of extending immunological imprinting across all currently circulating strains and against potential pandemic strains of influenza A virus, potentially providing a readily accessible form of universal protection against severe disease from both pandemic and seasonal influenza.