Fc functional antibodies in humans with severe H7N9 and seasonal influenza

Hillary A Vanderven; Lu Liu; Fernanda Ana-Sosa-Batiz; Thi Ho Nguyen; Yanmin Wan; Bruce Wines; P Mark Hogarth; Danielle Tilmanis; Arnold Reynaldi; Matthew S Parsons; Aeron C Hurt; Miles P Davenport; Tom Kotsimbos; Allen C Cheng; Katherine Kedzierska; Xiaoyan Zhang; Jianqing Xu; Stephen J Kent

doi:10.1172/jci.insight.92750

Fc functional antibodies in humans with severe H7N9 and seasonal influenza

JCI Insight. 2017 Jul 6;2(13):e92750. doi: 10.1172/jci.insight.92750.

Authors

Hillary A Vanderven¹, Lu Liu², Fernanda Ana-Sosa-Batiz¹, Thi Ho Nguyen¹, Yanmin Wan², Bruce Wines³, P Mark Hogarth³, Danielle Tilmanis⁴, Arnold Reynaldi⁵, Matthew S Parsons¹, Aeron C Hurt⁴, Miles P Davenport⁵, Tom Kotsimbos⁶, Allen C Cheng⁷, Katherine Kedzierska¹, Xiaoyan Zhang², Jianqing Xu², Stephen J Kent^{1

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Affiliations

¹ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
² Shanghai Public Health Clinical Centre (SPHCC) and Institute of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of the Ministry of Education/Health, Shanghai Medical College, Fudan University, Shanghai, China.
³ Burnet Institute, Melbourne, Victoria, Australia.
⁴ WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
⁵ Infection Analytics Program, Kirby Institute for Infection and Immunity, University of New South Wales Australia, Sydney, New South Wales, Australia.
⁶ Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia.
⁷ Infection Prevention and Healthcare Epidemiology Unit, Alfred Health and School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
⁸ Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
⁹ ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Victoria, Australia.

Abstract

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.

Funding: The National Health and Medical Research Council ([NHMRC] grants 1023294, 1041832, and 1071916), the Australian Department of Health, and the joint University of Melbourne/Fudan University International Research and Research Training Fund provided funding for this study.

Keywords: Immunology; Infectious disease.