Large-Scale Computational Modeling of H5 Influenza Variants Against HA1-Neutralizing Antibodies

Abstract

In June 2024, the U.S. Department of Agriculture released a report that showed over 300 samples from 2022-2024 of highly pathogenic avian influenza have been detected in mammals (1). To date, the World Health Organization reports that there have been approximately 5 humans infected with H5N1 in 2024, but the broader potential impact to human health remains unclear. In this study, we computationally model 1,804 protein complexes consisting of various H5 isolates in 1959 to 2024 against 11 HA1-neutralizing antibodies. This study shows a trend of weakening binding affinity of existing antibodies against H5 isolates over time, indicating that the H5N1 virus is evolving immune escape of our medical defenses. This study also showcases the value of high-performance computing to rapidly model protein-protein interactions at-scale for functional insights into medical preparedness.