AI Reveals H5N1 Virus Evolving to Evoke Stronger Immune Evasion, Raising Pandemic Concerns

The H5N1 avian influenza virus, which primarily infects birds and mammals, has shown a concerning trend toward increased immune evasion. As of June 2025, the virus has infected 70 people and caused one fatality in the United States. Researchers at the University of North Carolina at Charlotte (UNCC) have leveraged artificial intelligence (AI) to analyze the virus's evolving strategies, revealing critical insights into its pandemic potential. Colby T. Ford, Ph.D., a computational biologist at UNCC, led the study alongside Shirish Yasa, B.S., who contributed as an undergraduate and is now studying at Eastern Virginia Medical School. They presented their findings at the 2025 ASM Microbe conference, the annual meeting of the American Society for Microbiology, held in Los Angeles. The team collected data on over 1,800 H5N1 proteins and utilized AlphaFold 3, an advanced AI protein folding system, to predict the complex structures of these viral proteins. By applying physics-based modeling, they tested the binding efficiency of 11 immune antibodies, sourced from both humans and mice, to these proteins. The results were stark: the virus’s ability to attach to these antibodies has diminished over time, indicating an enhanced capability to evade natural human immune defenses. "The virus has mutated significantly from what we observed a decade ago," Ford noted. "It looks almost unrecognizable compared to earlier strains." This mutation pattern suggests that vaccines developed 10 years ago might no longer be effective against the current variants of H5N1, raising serious concerns about the virus's pandemic potential. To delve deeper into the virus's transmission dynamics, the researchers have been analyzing large datasets to map distinct clades of H5N1 to specific transmission routes. Their analysis has identified different clades with varied pathways for host-to-host transmission. For instance, they linked a recent H5N1-related death in Louisiana to a clade capable of direct bird-to-human transmission, bypassing other intermediate hosts. These findings underscore the virus's sophisticated methods of immune system evasion and highlight the role of AI in tracking its evolution. Moreover, the research points to the possibility of designing more effective antibodies and therapeutics by leveraging molecular information from new and emerging strains. "We are exploring the use of our AI pipeline to develop novel therapeutics specifically targeting these new strains," Ford explained. "The preliminary results are promising, and we believe this approach can significantly accelerate the development of effective treatments." In summary, the H5N1 avian influenza virus continues to evolve, posing a growing threat to public health. However, the integration of AI and computational modeling offers a powerful tool for researchers to monitor these changes and develop innovative solutions to combat the virus.