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

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 ADC...

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Published in:The Journal of infectious diseases 2016-09, Vol.214 (6), p.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: Article
Language:English
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
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Summary: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.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiw262