The Birth of Influenza Immunity: High-Resolution Antibody Dynamics Driven by Maternal Antibody Waning, Vaccinations, and Infections during the first Two Years of Life

Although infants are often described as immunological clean slates, the magnitude and durability of their first immune responses, and their effects on subsequent exposures, remains unclear. We conducted a longitudinal study of n=245 children across their first two years of life, mapping influenza antibody dynamics following vaccinations and infections. Maternal antibodies efficiently transferred to infants but exhibited different kinetics, with influenza B antibodies persisting longer than influenza A (half-life{approx}75 vs 50 days). Among infants whose maternal antibodies did not fully decay by the time of their 1st vaccination, 83-94% had no influenza A response while 59-72% had no influenza B response. To account for such maternal interference in infant vaccine responses, we formulated a personalized clinical algorithm that uses a single maternal blood draw and antibody half-lives to predict when maternal antibodies will reach undetectable levels. In addition, antibody responses varied across vaccine strains, with most infants exhibiting no response to H1N1 or H3N2 during 1st vaccination but eliciting a response after 2nd vaccination. Consequently, infants that turned 6 months old and were vaccinated in February-May - after the peak in influenza cases - showed enhanced antibody titers the following season, suggesting that [~]33% of infants in this category may benefit from late-season vaccination. Across the 60 infections captured, influenza A infections elicited strong, subtype-specific responses while influenza B led to weaker but more cross-reactive responses. Irrespective of prior infections, a strong 1st vaccine response was a predictor of a strong 2nd vaccine response, suggesting that the 1st vaccine response influences subsequent influenza immunity.