Analysis of live-attenuated influenza vaccine responses in the blood and tonsils of intranasally immunized children and adults 4275

Abstract Description Developing vaccines that elicit protection at the natural site of infection is desirable for optimal immunity. One such strategy is the use of live-attenuated influenza vaccines (LAIV), which are delivered intranasally and are typically given to children. However, the underlying mechanisms by which they induce protection are unclear and difficult to quantify from peripheral blood. Therefore, we studied the ongoing immune response in the tonsils and autologous blood from children and adults immunized with LAIV 5-10 days prior to tonsillectomy. Blood analyses showed increases in hemagglutination titers in most donors following vaccination. Next, using a tonsil organoid model, we restimulated these LAIV-vaccinated tonsil cells with influenza vaccines and viruses to identify antigen-specific B cell responses. Restimulated conditions elicited germinal center responses highest in seroconverting donors. Interestingly, most responses were non-neutralizing to H1 virus challenge in vitro despite prior exposure to the strain-matched antigen through vaccination. Altogether, our findings show that tonsil organoids reflect in vivo responses to LAIV immunization and provide a platform to challenge and study LAIV-induced protection. These results suggest that studying both clinical and tissue immune responses to influenza vaccination are essential to evaluating vaccine effectiveness. Funding Sources Supported by NIH/NIAD 5T32AI007319-35; NIH/NIAD 5R01AI173023-02; NIH Clinical and Translational Science Award (CTSA); Wellcome LEAP (Wellcome Trust, UK) Topic Categories Mucosal and Regional Immunology (MUC)