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Newswise — From egg prices to pet food recalls – and now, confirmation that has infected a large commercial flock of broiler chickens on a Mississippi farm – headlines are capturing escalating concern over H5N1’s spread.

According to  by a team of bioinformatics and genomics experts at the University of North Carolina at Charlotte, the virus has already adapted itself to escape immunological defenses (such as those raised by previous infection or vaccination) in mammals. The risk to human health is expected to rise as H5N1 evolves to better infect mammals, the study finds.

This rapid adaptation means that “an H5N1 vaccine made (for an earlier strain) will have less efficacy,” said Colby T. Ford,’14, ’15 M.S., ’18 Ph.D., now a visiting scholar in data science at UNC Charlotte’s Center for Computational Intelligence to Predict Health and Environmental Risks (). 

The UNC Charlotte research could prove pivotal (just as a by the same group on COVID-19 mutations did several years ago) as global leaders weigh the public health response to avian influenza.

“We are entering a whole new era of molecular epidemiology in which we provide a functional insight above and beyond disease surveillance,” said Dan Janies, Ph.D., CIPHER co-director and the Carol Grotnes Belk Distinguished Professor in Bioinformatics and Genomics. 

“Large data sets can be analyzed rapidly with high-performance computing and artificial intelligence to assess our preparedness for important problems such as H5N1, which is spreading rapidly to new hosts and regions including American cattle and farmworkers.”

Janies and Ford, along with Bioinformatics Assistant Professor Richard Allen White III, Ph.D., led students Shirish Yasa, Khaled Obeid, and Sayal Guirales-Medrano in the groundbreaking study, published after peer review in eBioMedicine on March 17. 

Analyzing H5N1 antibody interactions

While avian influenza has yet to achieve human-to-human transmission, it is already considered a pandemic among animals. 

The virus has infected small mammals and hundreds of species of wild and domestic birds and in recent years H5N1 has expanded its reach to larger mammals, including cattle. This change in host range significantly increases the risk of human infection, particularly as the virus evolves to evade immune defenses.

As Ford explains, the weakening of antibody binding affinity to newer viral strains means that we could be facing an H5N1 strain capable of efficiently infecting humans, with potentially severe consequences.

Data and findings from the CIPHER team can help public health decision-makers be more forward-looking in the effort to contain H5N1.

“Through the large scale of high-performance and cloud computing, we employ AI and other modeling tools to answer such questions computationally,” Ford explains. “In this study, our aim is to be more forward-looking to predict the potential health impacts of H5N1 influenza before a major event catches us off guard.”

Avian influenza jump to cows, now humans

While many refer to the virus as simply “bird flu,” scientists have long surveilled avian influenza to find it is indeed a zoonotic virus – meaning it can and does hop from birds to mammals, such as cows and humans. UNC Charlotte’s research indicates current lineages of the virus are equally able to infect bird and mammal cells.

In fact, the most recent H5N1 strains show signs of the virus being able to replicate itself much more readily in mammals than previously known. 

The most up-to-date research from the team at UNC Charlotte documents H5N1’s “strengthening immune evasion capabilities.”

In a March 17 (undergoing peer-review), researchers explain that a specific gene of the virus has changed over time – allowing avian influenza to improve its ability to hijack mammalian cells.

Along with the earlier research published by eBioMedicine, the findings provide urgent insight as avian influenza poses an ongoing threat to global agricultural interests and raises increasing alarms for human health.

The team’s ability to model H5N1’s evolution in real-time measures how rapidly the virus can change, which is critical when it comes to anticipating and responding to public health threats.

As Janies points out: “When you’re studying something as fast-evolving as a virus, speed is essential.” 

Vaccine efficacy, infection control

At UNC Charlotte, faculty and student researchers have been analyzing avian influenza variants’ immunoprotein interactions for close to a year. 

Due to the computational tools they had assembled during the SARS-CoV-2 pandemic, the team first published pre-print findings on H5N1 viral lineages in July 2024 – just four months after a farmworker in Texas was confirmed to have been infected by a cow. 

Via high-performance computational modeling, the team analyzed over 1,800 viral protein-host antibody interactions to track how H5N1’s hemagglutinin (HA) proteins — the key components the virus uses to enter host cells — have evolved. Findings suggest the virus is increasingly capable of binding to antibodies generated from previous infections or vaccinations, signaling a weakening of the immune response over time.

“High-performance computational modeling is a pathway for chipping away at multiple angles of biological variation at speed and scale,” Janies said. “It helps us tune our intuition to the right approaches for vaccine efficacy and infection control as viruses evolve.”