Bird flu virus is rapidly evolving to evade immune defenses

A new study has found that the H5N1 avian influenza virus is mutating to evade immune defenses in mammals following prior infection or vaccination.

The research, led by UNC Charlotte, emphasizes the growing threat of H5N1 to both agriculture and public health.

“H5N1 can infect avian and mammalian livestock and jump to humans,” the authors wrote. highlighting that new strains appear increasingly resistant to existing antibodies. This evolution, they caution, suggests that older vaccine formulas may lose effectiveness.

“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 from our therapeutic and immunological defenses,” noted the researchers.

Rapid shifts in bird flu virus

By running large-scale computational models of specific viral proteins binding with neutralizing antibodies, the research team discovered “an overall worsening in antibody affinity to more recent H5N1 isolates.” 

“If one makes an H5N1 vaccine with a previous vaccine candidate virus, the vaccine will have less efficacy, based on our measurements of how much the virus has evolved in recent years,” explained lead author Colby T. Ford, a visiting scholar at UNC Charlotte’s Center for Computational Intelligence to Predict Health and Environmental Risks (CIPHER).

Conducted under the guidance of assistant professor Richard Allen White III, and CIPHER co-director Daniel Janies, the UNC Charlotte team joined forces with Massachusetts Institute of Technology (MIT) researchers Rafael Jaimes III and Phillip J. Tomezsko to explore how the H5N1 virus is adapting so quickly.

Mounting zoonotic risk

Analyzing 1,804 antigen-antibody interactions, the researchers examined how the virus’s hemagglutinin subunit changed from 1996 to 2018. 

By applying high-performance computational techniques, they tracked the virus’s “antigenic drift” – small cumulative mutations that hamper the effectiveness of immune defenses from earlier infections or vaccines.

The new measurements of how much the bird flu virus has evolved in recent years confirmed that H5N1 is becoming less recognizable to established antibodies.

“These results indicate that the virus has potential to move from epidemic to pandemic status,” wrote the researchers.

Emergence across multiple species

Though H5N1 has primarily circulated in birds, it has jumped to mammals and, rarely, to humans. 

In the past year, the virus was found in dairy cattle in at least 17 U.S. states, and the Centers for Disease Control and Prevention (CDC) reported 70 human cases, including one fatality, in the United States since January 2022. 

Worldwide, according to the World Health Organization, H5N1 has been linked to 466 human deaths since 2003.

Between January 2022 and March 2025, the CDC also documented 12,510 H5N1 outbreaks among wild birds within the U.S., virus detections in 51 jurisdictions and 166,417,923 affected poultry.

Such widespread, cross-species infections strongly indicate that avian influenza can be considered a pandemic among animal populations, raising fears of a future human pandemic.

Birds flu vaccination and public health

In discussing how to avert the looming threat, the authors argue that a new approach to vaccine development may be needed. 

These findings indicate that once the bird flu virus modifies itself significantly, older vaccines will have less efficacy, making it essential to develop and regularly update H5N1 vaccines reflecting the virus’s continuous genetic changes.

Furthermore, the study’s results highlight the power of high-performance computing in mapping viral evolution. By integrating AI-based protein folding with physics-based simulations, researchers can anticipate changes in viral structure and better inform policy decisions. 

Bird flu’s potential for pandemic status

With H5N1 already widespread among wild birds and expanding its foothold in mammalian hosts, the virus’s cross-species jumps present a significant concern. 

According to the experts, more robust monitoring, updated vaccination strategies, and ongoing computational analyses will be crucial in mitigating a potential outbreak. 

As Janies concluded, computational modeling can help experts “tune our intuition to the right approaches” for vaccine design and intervention strategies before a fast-adapting virus gains an uncontrollable edge.

The study is published in the journal eBioMedicine. 

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