Welcome to the New York Influenza Center of Excellence (NYICE) NYICE Contract Number:HHSN272201400005C NYICE is a multidisciplinary, multi-institutional, center that emphasizes basic and clinical research on human influenza surveillance, pathogenesis, and host responses to infection and vaccination. Research in the NYICE focuses on clinical studies of influenza infection and vaccination in partnership with immunologists, virologists, and computational biologists. The focus of our center is on the fundamental question of why immune protection from influenza often fails, even in individuals who have generated an apparently robust immune response following infection or vaccination. As part of our surveillance activities, we will collect and analyze the viruses causing influenza infections in vaccinated and unvaccinated subjects and match these to the antibody responses present before infection or at the time illness begins. We will also study the impact of the infections or vaccination on the responding B cell and immunoglobulin (antibody) specificity and function, including development of memory. We will also investigate the nature of T cell help for B cell responses, including antigen presentation and peptide specificity. Optional activities will expand the number of samples available and provide information about the consequences of infection and disease impact, provide additional insight into the role of the innate response in controlling infection and the response to vaccination, and the potential for differences in HA cleavage to account for varying pathogenesis. Overall, these studies address the key question whether vaccine failure results from poor match of the infecting virus and immunity, aspects of the virus, and/or deficiencies in the immune responses to vaccination and infection. The paragraphs below briefly describe the research projects envisioned by NYICE.