PROJECT SUMMARY/ABSTRACT This F31 project aims to close gaps in knowledge that could inform vaccine policy and facilitate implementation of maternal influenza vaccines in low- and middle-income countries (LMICs). Influenza causes 3-5 million cases of severe illnesses and 290,000-650,000 deaths globally each year. Pregnant people are at increased risk of influenza morbidity and mortality, making vaccination a high priority in this population to protect themselves, their fetuses, as well as their infants via maternal antibodies. Although influenza mortality rates are estimated to be higher in LMICs, empiric data on the influenza disease burden are limited. In addition, the impact of maternal influenza vaccination on infant growth has not been evaluated while accounting for bias induced by undefined infant growth outcomes due to fetal or early infant death. Best practices for implementing maternal immunization programs have also not been established including the optimal timing of vaccination. Moreover, potential costs must be considered since LMIC health budgets often need to prioritize which interventions to implement due to resource constraints. The proposed F31 research project leverages data collected between 2011-2014 as part of a maternal influenza vaccine RCT in Sarlahi District, Nepal (NCT01034254) among pregnant people (18-40 years) and their infants who were followed through 6-months postpartum. The parent study included enrollment visits, weekly household-based active surveillance for respiratory pathogens, illness surveys on symptoms and care seeking behaviors, maternal/infant birth assessments, monthly maternal comorbidity assessments, and infant anthropometry visits at birth and 6 months to measure weight (g), length (cm), and head circumference (cm). Using log-binomial regression methods, Aim 1 will assess the impact of influenza vaccination during pregnancy on maternal influenza disease severity among pregnant participants (n=3693). Aim 2 will characterize the effect of maternal influenza vaccination on infant z-scores at birth and 6 months of age accounting for outcomes truncated by death among all singleton births using multinomial logistic regression (n=3520). Aim 3 will evaluate the optimal timing and cost-effectiveness of administering seasonal influenza vaccine during pregnancy using an existing decision tree model to project the potential impact of maternal influenza vaccine timing strategies (second versus third trimester compared to no vaccination) and calculate incremental cost- effectiveness ratios. Data generated from this project will expand the current maternal influenza vaccine evidence base in LMICs, which may motivate changes in vaccine policy, implementation, and investment decisions. As a long-term goal, the F31 study team seeks to contribute to reducing disparities in global influenza vaccine access so that all communities can benefit from this critical public health intervention. This research plan will provide ...