Recent research conducted at the Perelman School of Medicine at the University of Pennsylvania has uncovered that prior exposure to certain seasonal influenza viruses could lead to the development of cross-reactive immunity against the H5N1 avian influenza virus. The study indicates that older adults who encountered seasonal flu viruses before 1968 are likelier to possess antibodies that can attach to the H5N1 avian flu virus. This research was published in Nature Medicine and points to a significant generational disparity in immune protection against this strain of bird flu, underscoring the increased benefits of H5N1 vaccinations for younger adults and children, even those vaccines not explicitly tailored to the current strain circulating among birds and cattle.
Scott Hensley, PhD, a professor of Microbiology and the study’s senior author, elaborated on the findings, highlighting that immune responses triggered by influenza exposures in early childhood could last a lifetime. He explained that antibody responses initiated by exposure to H1N1 and H3N2 viruses several decades ago show the ability to cross-react with contemporary H5N1 avian viruses. While these antibodies may not prevent infection entirely, they are likely to mitigate the severity of the disease should an H5N1 pandemic occur.
The research sheds light on these antibodies’ potential protective role against a rapidly mutating virus. The H5N1 viruses have been present in birds for many years; however, a new variant known as clade 2.3.4.4b H5N1 virus has recently emerged and spread among cattle. This new strain poorly binds to receptors in the human upper respiratory system. Still, its extensive circulation among mammals might lead to mutations that could enhance its ability to infect human airway cells and potentially facilitate human-to-human transmission.
Influenza viruses possess surface proteins called hemagglutinin and neuraminidase, which enable the virus to attach to and infect healthy cells. The study involved testing blood samples from individuals born between 1927 and 2016 for antibodies that target the stalks of these proteins, particularly the less frequently evolving stalks of the hemagglutinin protein. The findings revealed that older adults born before 1968, likely exposed to H1N1 or H2N2 in their childhood, exhibited elevated levels of antibodies capable of binding to the stalk of the H5N1 virus. In contrast, young children not exposed to these older viruses displayed significantly lower protective antibodies against H5N1.
The researchers also explored how individuals from different generations responded to H5N1 vaccinations by examining blood samples taken before and after these individuals were vaccinated with a 2004 H5N1 vaccine that did not precisely match the clade 2.3.4.4b H5N1 virus currently in circulation. Before vaccination, older adults already had higher antibodies capable of binding to H5 stalks. After immunisation, while there was only a slight increase in these antibodies among older adults, there was a substantial increase in children, indicating that the vaccine effectively enhanced their immune response against both the 2004 virus and the current clade 2.3.4.4b virus.
Concluding his remarks, Hensley stressed the potential widespread susceptibility to an H5N1 pandemic across all age groups but noted that the most significant impact might be on children. He advocated prioritising children in H5N1 vaccination efforts, especially in preparation for potential pandemic scenarios. This reflects the crucial role vaccinations might play in controlling the spread of this adaptable and potentially deadly virus.
More information: Scott Hensley et al, Immune history shapes human antibody responses to H5N1 influenza viruses, Nature Medicine. DOI: 10.1038/s41591-025-03599-6
Journal information: Nature Medicine Provided by University of Pennsylvania School of Medicine
