New research from the La Jolla Institute for Immunology (LJI) suggests that many individuals may already have immune cells ready to combat the H5N1 virus, also known as highly pathogenic avian influenza, which has caused concern since its emergence in 2022.
H5N1, commonly referred to as “bird flu,” has spread widely among animal populations, particularly in poultry and cattle. The U.S. Centers for Disease Control and Prevention (CDC) reported 66 confirmed cases of H5N1 infections in U.S. poultry and dairy workers, who contracted the virus through contact with animals. Notably, there have been no confirmed instances of human-to-human transmission so far.
LJI scientists, including Professor Alessandro Sette, Dr. Biol. Sci., and Research Assistant Professor Alba Grifoni, Ph.D., have been closely monitoring the evolving virus. In a recent study published in mBio, the team compared genetic sequences of H5N1 to those of seasonal influenza viruses that are already circulating in humans.
The researchers discovered significant genetic similarities between H5N1 and common influenza strains, suggesting that many people might already possess “cross-reactive” T cells—immune cells that are on standby to target and fight H5N1 should it mutate to become a more widespread threat to human health.
“This makes us believe that a certain number of cross-reactive T cell responses may already be in place and may help decrease disease severity,” said Sette, also Co-Director of the LJI Center for Vaccine Innovation.
How the Study Worked
Most individuals in the U.S. have either contracted the flu in the past or received flu vaccinations. This exposure has helped their immune systems develop a level of immunity to common influenza viruses.
Sette and Grifoni’s research focused on how well these influenza-fighting T cells might recognize and target the new H5N1 virus. The scientists used data from the Immune Epitope Database (IEDB), led by LJI, to pinpoint how human T cells attack key proteins, known as epitopes, on seasonal flu viruses. They then developed a computational approach to see if the H5N1 virus shared these same vulnerable epitopes.
The team discovered that many epitopes are conserved between H5N1 and seasonal influenza viruses. As a result, a substantial portion of the population may already have T cells that are primed to combat H5N1 infections.
“We can predict that – in the majority of cases – our T cells have memory responses and can provide pre-existing immunity to H5N1. That’s good news,” said Grifoni.
Next Steps for Understanding H5N1 Infections
While the researchers cannot definitively conclude that these cross-reactive T cells will lessen disease severity, previous studies from LJI scientists have shown that such immune responses have helped reduce the severity of other infections, such as COVID-19 and mpox.
Looking ahead, the researchers are keen to further study the strength and effectiveness of these T cell responses. They also plan to analyze immune cells from human samples in the event that H5N1 begins to spread between people.
“We need to continue to monitor the situation, and if an outbreak were to occur, we’re ready to examine immune responses in more detail,” Sette noted.
Though rare, there have been instances in the past where other avian influenza A viruses, distinct from H5N1, have spread between humans. However, these occurrences have been infrequent, reinforcing the importance of continued surveillance and research.
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