Predicting H5N1 disease severity based on T cell responses

Predicting H5N1 disease severity based on T cell responses

New research led by scientists at the La Jolla Institute for Immunology (LJI) suggests that many people already have immune cells ready to fight the H5N1 virus, also known as highly pathogenic avian influenza.

The H5N1 “bird flu” virus emerged in 2022 and has spread widely in animal populations, including poultry and cattle. According to the US Centers for Disease Control and Prevention, there have been 66 confirmed H5N1 infections [as of Dec. 31, 2024] in poultry and dairy workers in the USA who became infected with the virus through animal contact. To date, there are no known cases of human-to-human transmission.

LJI scientists and vaccine experts are closely monitoring the emerging virus. In a new onemBioIn a study, LJI Professor Alessandro Sette, Dr.

The LJI team discovered key similarities between H5N1 and these common viruses, allowing them to predict that many people already have "cross-reactive" T cells ready to attack H5N1 if it ever mutates and causes widespread disease in humans.

“This leads us to believe that a certain number of cross-reactive T cell responses may already be present and can help reduce disease severity,” says Sette, who also serves as co-director of the LJI Center for Vaccine Innovation.

How the new study worked

Most Americans have had the flu or received a flu shot in the past. This means that their immune system has built up some immunity to common influenza viruses.

Sette and Grifoni examined how well these flu-fighting T cells could recognize and fight the new H5N1 virus. The scientists used data from the LJI-led Immune Epitope Database (IEDB) to identify exactly how human T cells attack key proteins or epitopes of seasonal flu viruses. They then developed a computational approach to find out whether the H5N1 virus had the same susceptible epitopes.

The researchers found that many epitopes are shared or “conserved” between H5N1 and seasonal influenza viruses. This means that many people may already have T cells equipped to fight H5N1 infections.

We can predict that in most cases our T cells have memory responses and can provide pre-existing immunity to H5N1. That’s good news.”

Alba Grifoni, research assistant professor, La Jolla Institute for Immunology

Next steps in understanding H5N1 infections

Researchers cannot say with certainty whether these T cell responses can reduce the severity of the disease; However, there is reason to believe that cross-reactive T cells could be good fighters. In previous studies, LJI scientists have shown that cross-reactive T cells can reduce the severity of COVID-19 and even MPOX.

In the future, researchers are interested in studying the strength of these T cell responses. They are also prepared to analyze immune cells from human samples should H5N1 spread between people.

“We need to continue to monitor the situation, and if an outbreak occurs, we will be ready to study immune responses in more detail,” says Sette.

According to the CDC, in addition to H5N1, there have been avian influenza A viruses that have spread between humans in the past, but this is very rare.

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