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

• Published in: The Journal of infectious diseases Vol. 214; no. 6; pp. 945 - 952
• Main Authors: Jegaskanda, Sinthujan, Luke, Catherine, Hickman, Heather D., Sangster, Mark Y., Wieland-Alter, Wendy F., McBride, Jacqueline M., Yewdell, Jon W., Wright, Peter F., Treanor, John, Rosenberger, Carrie M., Subbarao, Kanta
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15-09-2016
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Viral - immunology; Antibody-Dependent Cell Cytotoxicity; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H3N2 Subtype - immunology; Influenza Vaccines - immunology; Influenza virus; Influenza, Human - immunology; Major and Brief Reports; Male; Middle Aged; Orthomyxoviridae; PATHOGENESIS AND HOST RESPONSE; Pneumoviridae; Young Adult; USA, Wisconsin; influenza; vaccine; immunity; ADCC
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiw262

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.