Age-associated cross-reactive ADCC toward 2009-pandemic influenza

Background.?During the 2009 H1N1 influenza pandemic older individuals were partially protected from severe disease. It is not known whether pre-existing antibodies with effector functions such as antibody-dependent cellular cytotoxicity (ADCC) contributed to the immunity observed.Methods.?We tested sera from 182 individuals aged 1-72 years collected either immediately prior to, or following, the 2009-H1N1 pandemic for ADCC antibodies to the A(H1N1)pdm09 haemagglutinin(HA) protein.Results.?A(H1N1)pdm09 HA-specific ADCC antibodies were detected in almost all individuals in the >45 age group (28/31 subjects) prior to the 2009-H1N1 pandemic. Conversely, only approximately half of the individuals aged 1-14 (11/31) and 15-45 (17/31) had cross-reactive ADCC antibodies prior to the 2009-H1N1 pandemic. The A(H1N1)pdm09-specific ADCC antibodies were able to efficiently mediate the killing of influenza-infected respiratory epithelial cells. Further, subjects >45 years of age had higher ADCC to a range of seasonal H1N1 HA proteins, including from the 1918 virus, compared to younger individuals.Conclusions.?ADCC antibodies may have contributed to the protection exhibited in older individuals during the 2009-H1N1 pandemic. This work has significant implications for improved vaccination strategies for future influenza pandemics.