Background: There is an urgent need to understand the immune correlates of protection against avian influenza viruses (AIV), where pre-existing immunity may be limited.
Methods: Here, we characterized the antibody response in 12 severely ill A(H7N9) patients and examined its association with early-life imprinting and clinical outcome.
Results: We find that A(H7N9) patients imprinted with A(H2N2) during early life show minimal H7-IgM and a rapid IgG response across diverse hemagglutinin subtypes. They also have more high avidity H7-antibodies compared to older or younger patients. Early antibody titers against seasonal H1, H3, and conserved stalk domains trend negatively with clinical severity in A(H7N9) infection, while an inverse pattern is observed following severe A(H1N1) infection, potentially suggesting a different mechanism of immune regulation between seasonal and avian influenza virus infections.
Conclusions: These data provide direct serological evidence that birth imprinting profoundly shapes the humoral immune landscape during zoonotic influenza infection and may influence subsequent disease outcome.
This study aimed to examine how a person’s first flu infection in early life affects their immune response to avian flu later in life. We analyzed the immune responses of 12 severely ill patients and found that the first flu virus a person encounters in early life shapes their defense decades later. Patients whose first childhood flu was a strain known as H2N2 developed faster, stronger, and more specific immune response against a different strain, known as H7N9. Also, patients with a stronger immune response against common seasonal flu tended to have milder avian flu illness. This shows that early immune memory affects flu severity later in life. This understanding may help identify high-risk groups during outbreaks and improve age-specific vaccination strategies.
© 2026. The Author(s).