Cross-reactive immunity against influenza viruses in children and adults following 2009 pandemic H1N1 infection

2009 H1N1 pandemic influenza (A(H1N1)pdm09) virus infected large numbers of people worldwide. Recent studies suggest infection with A(H1N1)pdm09 virus elicited cross-reactive anti-hemagglutinin (HA) memory B cell response to conserved regions of HA. However, the breadth and magnitude of cross-reactive immunity in children and adults following A(H1N1)pdm09 infection are unknown. Methods: We investigated serum anti-HA immunity to a number of group-1 and -2 viruses in children and adults using hemagglutination inhibition (HAI), enzyme-linked immunosorbent assay and virus neutralization assay. Results: Applying hemagglutination inhibition (HAI) titers ≥40 against A(H1N1)pdm09 as threshold of sero-positivity, we observed significantly higher levels of anti-HA antibodies to a number of virus subtypes, including those neutralizing H5N1, in subjects with HAI titer ≥40 than those with HAI <40. Adults demonstrated broader and stronger cross-reactive anti-HA antibodies than children, including cross-reactive anti-HA1 and -HA2 antibodies. By comparison, individuals with serologic evidence of recent exposure to seasonal H1N1 or H3N2 did not show such broad cross-reactive immunity. Conclusion: Our results suggest individuals exposed to A(H1N1)pdm09 virus developed a broad and age-associated cross-reactive anti-HA immunity which may have important implications for future vaccination strategies to enable protection against a broader range of influenza viruses.