Immune Responses to the 2009 Pandemic H1N1 Virus As part of our investigations into immune protection from influenza, we have developed a series of related research projects focused on understanding how immune responses to the novel H1N1 influenza virus that emerged in 2009 (pH1N1) to cause a worldwide pandemic. In human subjects, we are investigating pre-existing immunity that cross-reacts with the pH1N1 virus. The focus here has been on T cells that respond to the virus itself, or to small pieces of the viral proteins (called epitopes) that are conserved among recent seasonal influenza viruses and the pH1N1 virus. These studies are split into studies of immune specificity (Mitra Azadniv) and function (Kristin Scheible). This includes identifying new epitopes in the pH1N1 virus that are not conserved, and can stimulate new immune cells uniquely reactive to the pH1N1 virus in subject that have been infected with the new strain. We are actively studying B cells, which make antibodies to fight the virus, in experimental clinical studies of pH1N1 and other emerging influenza strains (Jane Baer, Felix Santiago). Finally, we have developed animal models of pH1N1 infection that allow us to better understand how prior influenza infections and individual immune mechanisms provide optimal immune protection against the pH1N1 virus (Hailong Guo). Effector cytokine profiles determined by flow cytometry for human CD8+ T cells in response to pandemic (H1N1) or a recent seasonal (New Cal) varieties of H1N1 influenza virus. These results are from a subject who has not yet been exposed to the pandemic strain of the virus, and demonstrates that people may carry T cells that can cross-react to the novel influenza strain. Though the functional profiles are limited, with most cells producing one or two cytokines, these observations suggest that adults have immune cells that could provide a measure of protection against the virus (data is from K. Scheible).