Vaccine escape and zoonotic risk in evolutionary future of H5N1 influenza virus: UNC Charlotte study

Computational modelling of immunoprotein interactions of variants of avian influenza has shown that H5N1 virus has begun to evolve such that it will soon be able to escape human immunological responses raised by previous infections or vaccinations.

The findings of a research team from the University of North Carolina at Charlotte provides indicative evidence that avian influenza poses a significant ongoing threat to global agricultural and increasing the need to sound alarms for human health. 

“[The] overall worsening in antibody affinity to more recent H5N1 isolates indicates current and future H5N1 viral lineages pose an enhanced risk to human health,” explained Dr. Colby T. Ford, lead author and a visiting scholar in data science at UNC Charlotte’s Centre for Computational Intelligence to Predict Health and Environmental Risks (CIPHER).

This may include the possibility of increased transmission in humans, given that rapid adaptation means: “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,” said Ford.

‘Low-sugar’ vaccine offers broad coronavirus variants immunity

Being sugar-coated doesn’t just help the medicine go down, as the song goes, but it can also help a virus evade the immune system. However, researchers have now developed a universal vaccine th... Read More

The team’s approach provides guidance for how to keep pace with a rapidly changing threat from H5N1. By examining the virus’ host-shifting and recent mutations, researchers found that: “the continuous transmission of H5N1 from birds to mammals and the increase in strains with immuno-evasive hemagglutinin (HAx) in mammals [when] sampled over time suggest that antigenic drift is a source of [increased] zoonotic risk.”

In the paper: “Large-scale computational modelling of H5 influenza variants against HA1-neutralising antibodies,” the UNC Charlotte research team shared their results from analysis of 1,804 viral protein-host antibody comparisons.

The experiments consisted of current HA domain 1 viral proteins computationally bound in physics models to neutralising antibodies obtained from infected hosts and vaccine recipients from 1996 to 2018. 

Using high-performance computational modelling, CIPHER researchers documented ‘a trend of weakening binding affinity of a wide variety of existing antibodies, collected from vaccinated and or infected hosts, against H5 viral isolates over time.’

The findings were made available through preprint publication in July 2024 – due to the public health importance of the findings – prior to its successful peer review.

The team was able to complete their work on H5N1 in just three months after the first reported cow-to-human transmission of H5N1, of a farmworker in Texas, having developed the computational tools during the COVID-19 pandemic.

In assessing the possible pandemic risk spurred by H5 bird flu spread and mutation, global researchers agree that ‘the avian virus (remains) high on lists of potential pandemic agents,’ as reported in Science in December 2024.

No human-to-human transmission has to date been reported. However, cattle in at least 17 states in the USA have tested positive for H5N1, in addition to the countless cases among wild birds, small mammals, commercial chickens and other farmed flocks.

Between January 2022 and March 2025, the US Centers for Disease Control reported:

• 12,510 known outbreaks among wild birds in the US.
• 51 jurisdictions with bird flu among wild birds.
• More than 166 million poultry birds affected.
• 70 human cases of H5N1, one of which was fatal.

Vaccines will be a crucial tool in controlling any future flu pandemic, according to expert consensus, as mutations of viral strains adapt to mammalian hosts.

Texas Biomed's candidate TB vaccine provides full cover in primates study

Tuberculosis vaccine shows superior immune response protection in nonhuman primates when compared to existing BCG vaccine A live-attenuated tuberculosis (TB) vaccine candidate in development... Read More

The Charlotte research team has written that their findings: “indicate that H5 [strains] have the potential to move from epidemic to pandemic status in the near future.”

The study – along with recent other research confirms that worsening antibody binding and greater avian-to-mammalian transmission – has indicated: “there is an impending danger to human health for highly pathogenic strains of H5 influenza that can infect avian and mammalian livestock and jump to humans.”

Avian influenza can already be considered a pandemic among both wild and domesticated animals due to the virus’ spread across geographies and species. Likewise, its spread from wild birds to chickens, dairy cattle and now farm workers shows its opportunism to jump across species.

The teams computational modelling results: “specifically assert that [this] worsening trend … is a cause for concern for [a] human pandemic.”

Further, the authors write that high-performance computing – which in this case included AI-based protein folding and physics-based simulations of viral protein-antibody interactions – provides rapid and reliable results to inform policy makers with regard to steps required for adequate pandemic preparedness. 

The team from UNC Charlotte’s Department of Bioinformatics and Genomics included students Shirish Yasa, Khaled Obeid, and Sayal Guirales-Medrano, led by Assistant Professor in Bioinformatics Dr. Richard Allen White III and Dr Daniel Janies, a co-director of CIPHER, and the Carol Grotnes Belk Distinguished Professor of Bioinformatics and Genomics. The UNC Charlotte team also collaborated with researchers from the Massachusetts Institute of Technology: Dr Rafael Jaimes IIIand dr. Phillip J. Tomezsko.

Meanwhile, in the United Kingdom the world’s first case of bird flu in a sheep has been detected. The H5N1 virus was detected in a single animal in Yorkshire, England, following precautionary routine testing because the flock was being kept on a site where avian influenza had previously been found in birds.

UK authorities announced that no other sheep in the flock were found to have been infected and that the infected animal was culled, further stressing that the risk to livestock and the general public remained low. Strict biosecurity measures also have been implemented to prevent any spread of disease.

Bird flu can cause severe illness – and even death – with changes in H5N1 being tracked by health agencies around the world amid fears it has the potential to develop into a pathogen that could trigger a human pandemic.

For further reading please visit: 10.1016/j.ebiom.2025.105632