Research Summary The objectives of DIVINCI are to study influenza infection from birth to examine the effect of first influenza exposure and subsequent exposures on the immune response. In this U01, we address fundamental questions about how initial and repeated influenza exposures through natural infections and/or vaccination shape infant and childhood immunity to influenza. The COVID-19 pandemic has created two main issues affecting DIVINCI: 1) reducing circulation of other respiratory viruses across the world creating uncommon exposure histories for babies born during DIVINCI enrollment and 2) increasing infection rates due to Omicron and likely other variants and therefore increasing rates of influenza-like illness in these communities and the need for clinical testing of respiratory specimens. To address the above problems, we propose to continue to enroll participants into the New Zealand and the Los Angeles cohorts for the next two years. In total, we propose to enroll 150 additional infants in the New Zealand cohort and continue enrollment efforts in Southern California. Additionally, the Supplement will cover the unanticipated costs of operating during a pandemic including the increase in the number of participants meeting our testing criteria and the need for higher level PPE.