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Generation and Protective Ability of Influenza Virus–Specific Antibody-Dependent Cellular Cytotoxicity in Humans Elicited by Vaccination, Natural Infection, and Experimental Challenge

2016; Oxford University Press; Volume: 214; Issue: 6 Linguagem: Inglês

10.1093/infdis/jiw262

1537-6613

Sinthujan Jegaskanda, Catherine J. Luke, Heather D. Hickman, Mark Y. Sangster, Wendy Wieland‐Alter, Jacqueline McBride, Jon W. Yewdell, Peter F. Wright, John J. Treanor, Carrie M. Rosenberger, Kanta Subbarao,

Monoclonal and Polyclonal Antibodies Research

Background. Nonneutralizing antibodies (Abs) involved in antibody-dependent cellular cytotoxicity (ADCC) may provide some protection from influenza virus infection. The ability of influenza vaccines to induce ADCC-mediating Abs (ADCC-Abs) in adults and children is unclear. Methods. We quantified ADCC-Abs in serum samples from adults who received a dose of inactivated subunit vaccine (ISV) targeting monovalent 2009 pandemic influenza A(H1N1) virus or live-attenuated influenza vaccine (LAIV) or who had laboratory-confirmed influenza A(H1N1) virus infection. We also measured ADCC-Abs in children who either received a dose of trivalent seasonal ISV followed by trivalent seasonal LAIV or 2 doses of LAIV. Finally, we assessed the ability of low and high ADCC-Ab titers to protect adults from experimental challenge with influenza A/Wisconsin/67/131/2005(H3N2) virus. Results. Adults and children who received a dose of ISV had a robust increase in ADCC-Ab titers to both recombinant hemagglutinin (rHA) protein and homologous virus–infected cells. There was no detectable increase in titers of ADCC-Abs to rHA or virus-infected cells in adults and children who received LAIV. Higher titers (≥320) of preexisting ADCC-Abs were associated with lower virus replication and a significant reduction in total symptom scores in experimentally infected adults. Conclusions. ADCC-Ab titers increased following experimental influenza virus infection in adults and after ISV administration in both children and adults.