Age-associated cross-reactive antibody-dependent cellular cytotoxicity to 2009 H1N1 influenza prior to the pandemic (P6160)

Abstract

Abstract During the 2009 H1N1 influenza pandemic (H1N1pdm) older individuals were partially protected from disease. Prior seasonal H1N1 infections likely played a role by the induction of neutralizing antibodies and T cell immunity towards 2009-H1N1pdm. Non-neutralizing antibodies with other effector functions such as antibody-dependent cellular cytotoxicity (ADCC) may have assisted in the immunity observed. We tested sera from a cohort of 177 individuals aged 1-72 years old for ADCC antibodies to H1N1pdm HA either immediately prior to, or following, 2009 H1N1 pandemic by our ADCC NK cell activation assay. Almost all individuals in the >45 age group (28/30 subjects) had ADCC antibodies towards the H1N1pdm prior to the 2009 H1N1 pandemic, whereas approximately half of the individuals in the 1-14 (11/32) and 15-45 (9/16) had ADCC antibodies prior to the 2009 pandemic. The H1N1pdm-specific ADCC antibodies were able to mediate the killing of H1N1pdm-infected respiratory epithelial cells. Additionally, ADCC to H1N1pdm HA correlated with ADCC to the antigenically similar 1918 HA protein in subjects post-2009 influenza pandemic and subjects >45 years had higher ADCC towards a range of seasonal H1N1 HA proteins compared to younger subjects. We conclude that ADCC antibodies may have contributed to the protection exhibited in older individuals during the 2009-H1N1 pandemic. This has significant implications for improved vaccination strategies against future influenza pandemics.