Health and Human Services (HHS) and the Biomedical Advanced Research and Development Authority (BARDA) have identified a severe pandemic influenza outbreak as one of the greatest threats to national and global security. The Centers for Disease Control (CDC) warn that viruses like H7N9 and H5N1, with fatality rates of approximately 40% and 60% respectively, could lead to catastrophic outcomes if they were to trigger a pandemic, with models predicting infection in one-third of the world’s population. This project focuses on advancing the development of CM-PW3, a broadly neutralizing, cross-reactive human monoclonal antibody for prophylactic use in high-risk populations, providing targeted, preemptive protection against both seasonal and pandemic influenza strains, including H1N1, H5N1, and H7N9. We will evaluate the most efficient and economic delivery of the antibody and determine the expected duration of protection. The overarching goal of this program is to develop CMPW3 to provide passive, immediate pre-exposure protection to at-risk individuals for an entire influenza season (or >4 months).