A groundbreaking study from the Perelman School of Medicine at the University of Pennsylvania reveals that older adults may have stronger immunity to the H5N1 avian influenza virus, due to previous exposures to specific seasonal influenza viruses. The findings, published today in Nature Medicine, show that individuals exposed to seasonal flu viruses circulating prior to 1968 are more likely to have antibodies that bind to the H5N1 avian flu virus. The research suggests that younger adults and children, who have not been exposed to these older strains, would benefit more from H5N1 vaccines, even those not tailored to the current circulating strain.
The study highlights how early childhood exposure to influenza viruses can generate immune responses that endure for a lifetime. According to Scott Hensley, PhD, senior author of the study and professor of microbiology at the University of Pennsylvania, “We found that antibody responses primed by H1N1 and H3N2 viruses decades ago can cross-react to H5N1 avian viruses circulating today.” Although most of these cross-reactive antibodies may not prevent infections entirely, they are likely to reduce the severity of disease during an H5N1 pandemic.
While H5N1 viruses have been circulating in birds for many years, a new variant, clade 2.3.4.4b, has emerged and spread among cattle. This strain does not easily bind to receptors in the human upper airway, limiting its ability to infect humans. However, as the virus circulates among mammals, it could mutate in ways that enable it to infect human airway cells, leading to human-to-human transmission.
Influenza viruses are characterized by two proteins—hemagglutinin (H) and neuraminidase (N)—which allow the virus to attach to and infect human cells. The “H” in H5N1 refers to hemagglutinin, a protein that undergoes frequent changes, allowing the virus to evade immune responses. The “N” stands for neuraminidase, which plays a key role in virus replication. Influenza vaccines primarily target hemagglutinin to prevent infection, but the protein’s frequent evolution can make it difficult for the immune system to keep up.
Researchers tested blood samples from over 150 individuals, ranging from those born between 1927 and 2016, to measure antibody responses targeting the stalk proteins of different influenza viruses, including H5N1. The results revealed that older adults born before 1968, who were likely first exposed to H1N1 or H2N2 in childhood, had higher levels of antibodies capable of binding to the stalk of the H5N1 virus. In contrast, younger children, who were not exposed to these seasonal flu viruses, exhibited low levels of antibodies that could fight H5N1.
To assess how different age groups respond to H5N1 vaccinations, researchers obtained blood samples from a separate group of individuals born between 1918 and 2003 before and after they received a 2004 H5N1 vaccine, which did not perfectly match the current circulating clade 2.3.4.4b strain.
Consistent with previous findings, older adults had higher levels of antibodies that could bind to H5 stalk proteins before vaccination. After receiving the vaccine, older adults showed a slight increase in H5 stalk antibodies, while children’s antibody levels rose substantially. These antibodies were able to bind both to the 2004 H5N1 virus and the current clade 2.3.4.4b H5N1 virus.
While all age groups are likely to be susceptible to an H5N1 pandemic, the study suggests that children could bear the highest disease burden. In light of these findings, Scott Hensley advises, “If this is the case, children should be prioritized for H5N1 vaccinations.” These insights underscore the importance of tailored vaccination strategies, particularly for younger populations, to better prepare for a potential H5N1 pandemic.
This study reveals that older adults may have a unique immunity to the H5N1 virus due to prior exposure to earlier seasonal influenza strains. The findings also stress the importance of prioritizing younger individuals for H5N1 vaccines in the event of a pandemic. These insights could guide future vaccine development and public health strategies aimed at mitigating the impact of H5N1 should it evolve into a more transmissible virus.
The study was co-authored by researchers at the University of Pennsylvania, with no conflicts of interest reported.
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