Human protection against bird flu may be easier than scientists previously thought, thanks to new findings about the core genetic makeup of the virus and one particular T cell that all of us have in our immune-system arsenal. This means that many of us will have some innate ability to fight off the virus, but also provides many new avenues to develop the first human vaccine.
Scientists from Australia’s La Trobe University have found that despite mutations and evolution of the highly pathogenic avian influenza (HPAI) H5N1 virus, which has decimated wild bird populations and the poultry industry over the last five years, 64% of the pathogen’s genetic makeup is highly conserved. Essentially, this means that while 36% of the H5N1 genetic code has diverged, or mutated, two thirds has not – which implies this unchanged genetic coding is serving an important function.
What’s more, the researchers found that a specific human T cell – the CD8+ “killer” lymphocyte – can recognize parts of the H5N1 virus and mount a defence without an individual having ever been exposed to the flu bug before. And because the CD8+ T cell response is triggered by molecules in the highly conserved part of the virus’ genetic code, it bodes well for developing a vaccine that won’t lose efficacy from season to season or with H5N1 mutations.
“If we could develop a new vaccine using these conserved molecules from inside the virus, we might be able to protect against lots of different flu viruses,” said first author Emma Grant, from La Trobe’s Institute for Molecular Science and the School of Agriculture, Biomedicine and Environment. “That’s the long-term goal.”
In the study, Grant and her team used extensive bioinformatics and sequence analysis to predict whether T cells would recognize H5N1 based on past data (not surprisingly, testing live H5N1 virus strains in a laboratory is very risky and therefore highly restricted). Using data on known CD8+ T cell epitopes – small fragments of viral proteins the immune cell can identify – the researchers found that around 60% of people would likely have some degree of pre-existing immunity to H5N1 due to CD8+ T cell virus recognition.
“Cases of H5N1 in humans are rare, but they do happen,” Grant said. “If human-to-human transmission or human infection of H5N1 becomes more common, these people may have some level of protection already, which may help prevent severe disease.”
But, there is a catch. While we all have these T cells, not everyone’s immune system will recognize H5N1 in the same way, due to differences in our human leukocyte antigen (HLA) type. Put simply, the HLA is a group of genes that act as an interpreter for the immune system – and we all have a unique makeup of HLA molecules. However, that 60% figure might be much higher, depending on other ways our complex immune system works to recognize foreign cells. There are other factors, too, such as previous influenza A infection likely to boost an individual’s chance of recognizing fragments of H5N1.
Nonetheless, it’s a significant step forward in understanding potential pre-existing immunity and how this can be harnessed to develop a vaccine based on these highly conserved viral epitopes that would deliver long-lasting protection against serious illness.
There have now been 67 known cases of HPAI H5N1 human infection in the US, including one death, and scientists are closely watching for viral mutations that could see it harness human-to-human transmission. However, this continues to be a challenge due to poor monitoring of existing outbreaks in cattle and poultry, and government bungles that has hampered critical research.
Interestingly, a H5N1 vaccine could even be more effective than the common seasonal flu jab, which instead targets three-to-four strains of the virus. Because influenza evolves rapidly, it hasn’t been possible to target any highly conserved genes; instead, it targets the hemagglutinin – the ‘H’ in flu viruses such as H5N1 – which is a protein present on the surface of the pathogen. And there are 18 known types of hemagglutinin.
“With each vaccine, we mount an immune response to the hemagglutinin in the vaccine, but once the virus has significantly mutated these proteins, our immune system can no longer recognize it,” she said.
While the 2024-2025 flu season has been the worst in decades in the US, anyone who has succumbed to the virus may have also inadvertently developed some level of H5N1 protection. And this latest research may help scientists develop an improved flu vaccine.
“T cells – our own immune cells that defend us against pathogens – can recognize viruses they’ve previously come into contact with,” Grant added. “If we can use this knowledge to develop vaccines using the parts of the virus that T cells recognize, we might be able to protect ourselves from future flu mutations.”
The research was published in the journal Clinical & Translational Immunology.
Source: La Trobe University
