Fc functional antibodies in humans with severe H7N9 and seasonal influenza

Vanderven, Hillary A., Liu, Lu, Ana-Sosa-Batiz, Fernanda, Nguyen, Thi H.O., Wan, Yanmin, Wines, Bruce, Hogarth, P. Mark, Tilmanis, Danielle, Reynaldi, Arnold, Parsons, Matthew S., Hurt, Aeron C., Davenport, Miles P., Kotsimbos, Tom, Cheng, Allen C., Kedzierska, Katherine, Zhang, Xiaoyan, Xu, Jianqing, and Kent, Stephen J. (2017) Fc functional antibodies in humans with severe H7N9 and seasonal influenza. JCI Insight, 2 (13). e92750. pp. 1-15.

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BACKGROUND. Both seasonal and novel avian influenza viruses can result in severe infections requiring hospitalization. Anti-influenza antibodies (Abs) with Fc-mediated effector functions, such as Ab-dependent cellular cytotoxicity (ADCC), are of growing interest in control of influenza but have not previously been studied during severe human infections. As such, the objective of this study was to examine Fc-mediated Ab functions in humans hospitalized with influenza infection.

METHODS. Serum Ab response was studied in subjects hospitalized with either pandemic H7N9 avian influenza virus in China (n = 18) or circulating seasonal influenza viruses in Melbourne, Australia (n = 16). Recombinant soluble Fc receptor dimer ELISAs, natural killer (NK) cell activation assays, and Ab-dependent killing assays with influenza-infected target cells were used to assess the Fc functionality of anti-influenza hemagglutinin (HA) Abs during severe human influenza infection.

RESULTS. We found that the peak generation of Fc functional HA Abs preceded that of neutralizing Abs for both severe H7N9 and seasonal influenza infections. Subjects who succumbed to complications of H7N9 infection demonstrated reduced HA-specific Fc receptor-binding Abs (in magnitude and breadth) immediately prior to death compared with those who survived. Subjects who recovered from H7N9 and severe seasonal influenza infections demonstrated increased Fc receptor-binding Abs not only against the homologous infecting strain but against HAs from different influenza A subtypes.

CONCLUSION. Collectively, survivors of severe influenza infection rapidly generate a functional Ab response capable of mediating ADCC against divergent influenza viruses. Broadly binding HA Abs with Fc-mediated functions may be a useful component of protective immunity to severe influenza infection.

Item ID: 56893
Item Type: Article (Research - C1)
ISSN: 2379-3708
Copyright Information: Open Access Via Publisher Website. JCI Insight is an open access journal. All research content is freely available immediately upon publication, and all articles published in JCI Insight are deposited in PubMed Central (PMC). Users are allowed to read, download, print, search, or link to the full texts of the articles under the "fair use" limitations of US copyright law.
Funders: University of Melbourne (UM), Fudan University (FU), National Health and Medical Research Council (NHMRC), Australian Department of Health
Projects and Grants: NHMRC 1023294, NHMRC 1041832, NHMRC 1071916, UM/FU International Research and Research Training Fund
Date Deposited: 16 Jan 2019 07:43
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320405 Humoural immunology and immunochemistry @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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