In June 2024, the United States Department of Agriculture released a report that showed over 300 samples from 2022-2024 of highly pathogenic avian influenza have been detected in mammals. To date, the United States Centers for Disease Control reports that there have been 13 humans infected with H5N1 in 2024. The broader potential impact on human health remains unclear. In this study, we computationally model 1,804 protein complexes consisting of various H5 isolates from 1959 to 2024 against 11 HA1-neutralizing antibodies. This study shows a trend of weakening of the binding affinity of existing antibodies against H5 isolates over time, indicating that the H5N1 virus is evolving immune escape of our medical defenses. We also found that based on the wide variety of host species and geographic locations in which H5N1 was observed to have been transmitted from birds to mammals, there is not a single central reservoir host species or location associated with H5N1´s spread. These results indicate that the virus is well on its way to moving from epidemic to pandemic status in the near future. This study illustrates the value of high-performance computing to rapidly model protein-protein interactions and viral genomic sequence data at-scale for functional insights into medical preparedness.