The generation and protective ability of influenza-specific antibody-dependent cellular cytotoxicity in humans elicited by vaccination, natural infection or experimental challenge

BACKGROUND:

?Non-neutralizing antibodies with antibody-dependent cellular cytotoxicity (ADCC) function may provide some protection from influenza infection. The ability of influenza vaccines to induce ADCC mediating antibodies (ADCC-Abs) in adults and children is unclear.

METHODS:

?We quantified ADCC-Abs in serum samples from adults who received a dose of monovalent 2009 H1N1 pandemic (H1N1pdm09) inactivated subunit vaccine (ISV), or live-attenuated influenza vaccine (LAIV) or had laboratory-confirmed H1N1pdm09 infection. We also measured ADCC-Abs in children who either received a dose of trivalent seasonal ISV followed by trivalent seasonal LAIV or two doses of LAIV. Finally, we assessed the ability of low and high ADCC-Abs titers to protect adults from experimental challenge with influenza A/Wisconsin/67/131/2005 (H3N2) virus.

RESULTS:

?Adults and children that received a dose of ISV had a robust increase in ADCC-Ab titers to both recombinant (r)HA protein and homologous virus-infected cells. There was no detectable increase in ADCC-Abs to rHA or virus-infected cells in adults and children that received LAIV. Higher (≥320) pre-existing ADCC-Abs were associated with lower virus replication and a significant reduction in total symptom scores in experimentally infected adults.

CONCLUSIONS:

?ADCC-Abs increased following experimental influenza virus infection in adults and ISV administration in both children and adults.