Many rigorous studies have shown that early childhood infections leave a lasting imprint on the immune system. The understanding of this phenomenon has expanded significantly since 1960, when Dr. Thomas Francis Jr first coined the term “original antigenic sin”, to account for all previous pathogen exposures, rather than only the first. Now more commonly referred to as “immune imprinting”, this effect most often focuses on how memory B-cell responses are shaped by prior antigen exposure, and the resultant antibodies produced after subsequent exposure to antigenically similar pathogens. Although imprinting was originally observed within the context of influenza viral infection, it has since been applied to the pandemic coronavirus SARS-CoV-2. To fully comprehend how imprinting affects the evolution of antibody responses, it is necessary to compare responses elicited by pathogenic strains that are both antigenically similar and dissimilar to strains encountered previously. To accomplish this, we must be able to measure the antigenic distance between strains, which can be easily accomplished using data from multidimensional immunological assays. The knowledge of imprinting, combined with antigenic distance measures, may allow for improvements in vaccine design and development for both influenza and SARS-CoV-2 viruses.