Pandemic Influenza Translational Research and novel universal countermeasure development

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Despite long-term investment, influenza continues to be a significant worldwide problem. Influenza A viruses (IAV) are significant human pathogens causing yearly epidemics and occasional pandemics. Past pandemics have resulted in significant morbidity and mortality. The 1918 influenza pandemic was thought to have resulted in the death of at least 675,000 people in the U.S. and 40 million people worldwide. Pandemics in 1957 and 1968, while less severe, were also of major public health importance. A novel influenza A virus of swine origin became pandemic in 2009, causing the first pandemic in 41 years. In addition, annual epidemic influenza cases are also very significant resulting in up to 49,000 deaths in the U.S. annually. We continue our human challenge work both developing novel challenge models and continuing to utilize our previously developed models fo H1N1 and H3N2. The SARS-CoV-2 pandemic limited our work with these models during 2020 and 2022 but we are now moving forward again in this post-pandemic period. We have completed analysis of a challenge study performed to evaluate mucosal immunity, which we will publish later this year. We are set to start a challenge study with a novel low pathogenesis avian influenza virus of subtype H10N7 in the first quarter of the next fiscal year, and we are in the process of putting together collaborations to study our 2013 Switzerland H3N2 challenge virus in humans in this next fiscal year as well. We continue to produce and maintain GMP manufactured useful challenge viruses including a pre-pandemic H1N1 and an influenza-B viruses. This past year we completed our collaboration with DMID where our H1N1 challenge virus and challenge protocol was used in a challenge study in the VTEU system. This has been instrumental in expanding challenge capacity in the U.S. and moving the influenza challenge field forward leading to other collaborations and larger programs. We continue with our serological studies including our long term study of individuals post participation in a challenge study. We also have completed a clinical study evaluating mucosal and systemic immunity in children after influenza vaccination that we expect to publish in the coming year as well as are continuing to enroll a longitudinal study of adults post COVID and Influenza vaccination to evaluate their mucosal and systemic responses, as well as the interactions between the two. In addition to these clinical studies we continued our collaborations with Stanford, FDA, and within NIAID to further study human influenza infection and how it relates to other viral infections.