New research suggests that past exposure to seasonal flu viruses may help protect people from severe illness caused by the H5N1 avian flu virus. Scientists at the Perelman School of Medicine at the University of Pennsylvania found that older adults who were exposed to flu viruses circulating before 1968 were more likely to have antibodies that recognize H5N1.
The study, published in Nature Medicine, highlights an important discovery: younger adults and children, who lack this natural immunity, may benefit more from H5N1 vaccines—even if those vaccines are not a perfect match for the current virus strain spreading in birds and cattle.
How Flu Exposure Shapes Immunity
According to the study’s senior author, Dr. Scott Hensley, the immune system remembers flu viruses from childhood. “Early childhood flu exposures create immune responses that last a lifetime,” he explained.
The researchers found that people who were first exposed to H1N1 or H2N2 flu strains in childhood—both common before 1968—had higher levels of antibodies that could recognize parts of the H5N1 virus.
However, these antibodies are not perfect at stopping infections. Instead, they may help reduce the severity of illness if H5N1 were to start spreading between humans.
The Risk of an H5N1 Pandemic
H5N1 has circulated in birds for years, but a newer version, called clade 2.3.4.4b H5N1, has recently spread to cattle. Right now, this strain does not easily infect humans because it does not bind well to airway cells in the upper respiratory tract. However, if the virus mutates in a way that improves its ability to infect humans, it could potentially trigger a pandemic.
Influenza viruses are named after two proteins on their surface: hemagglutinin (H) and neuraminidase (N). Hemagglutinin helps the virus attach to healthy cells and start an infection. Most flu vaccines work by prompting the immune system to produce antibodies that recognize and block this protein.
However, hemagglutinin is constantly evolving. The “head” of the protein changes frequently, while the “stalk” remains more stable. Researchers tested blood samples from over 150 people born between 1927 and 2016 to see whether they had antibodies targeting the stalk of the H5N1 virus.
They found that older adults—who were first exposed to earlier flu strains—had more antibodies that could recognize the H5 stalk. In contrast, young children, who had never been exposed to similar flu viruses, had very few of these antibodies.
Vaccines Work, Especially for Younger People
The researchers also studied how people with different birth years responded to an H5N1 vaccine. They analyzed blood samples from individuals born between 1918 and 2003 before and after they received a 2004 H5N1 vaccine.
As expected, older adults already had some H5 antibodies before vaccination. While their antibody levels increased slightly after vaccination, the biggest increase was seen in children. Importantly, these vaccine-induced antibodies were able to recognize both the older 2004 H5N1 virus and the newer clade 2.3.4.4b virus that is currently circulating.
Who Should Get Vaccinated in the Event of an Outbreak?
If H5N1 begins spreading between humans, all age groups will likely be at risk. However, Dr. Hensley believes the most severe cases may occur in children, who have little pre-existing immunity. “If this is the case, children should be prioritized for H5N1 vaccinations,” he said.
This research suggests that while older adults may have some level of immune protection due to past flu exposures, younger people are more vulnerable. In a future H5N1 outbreak, vaccines could be particularly important for protecting children and younger adults from severe illness.
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The research findings can be found in Nature Medicine.
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