Experimental live-attenuated influenza virus (LAIV) vaccines, delivered into the nose, have been shown protect pigs against influenza infection, more so than traditional inactivated commercial vaccines. In addition, LAIV vaccines have been shown to provide protection in piglets that have suckled from sows with influenza-specific immunity. Currently, inactivated vaccines are administered to sows thus, if a LAIV were to be used in piglets it is likely going to be administered in the presence of maternal-derived immunity (MDI). In addition, LAIV may be administered to sows in the future and it is important to understand the impact of MDI on LAIV vaccine efficacy in piglets. Data from a separate study suggests measuring antibody from LAIV vaccinated piglets with MDI may not be an effective measure of immunogenicity and cross-protection. The work in this proposal aimed to validate a live-animal assay that could be used as a predictor of vaccine-induced immunity and protection following LAIV vaccination in both MDI-positive and MDI-negative piglets. To these ends, sows were purchased and bred on-site, and vaccinated three times with either LAIV (4 sows) or WIV (4 sows), and naïve, non-vaccinated sows were purchased separately with similar farrowing dates. At three days of age, groups of piglets from sows were vaccinated intranasally with LAIV or non-vaccinated. At 42-days post vaccination blood, nasal wash, and oral fluids were collected from animals to evaluate the presence of IAV-specific immunity in piglets. Piglets were then challenged with influenza mismatched to the vaccine strain and vaccine efficacy was evaluated by measuring lung pathology and virus shedding in the nose, trachea, and lungs. Our results indicate that piglets were protected against influenza even when vaccinated in the presence of maternal immunity, but the ability to evaluate vaccination status was impeded by transferred maternal immunity.