Fc functional antibodies in humans with severe H7N9 and seasonal influenza

Hillary A. Vanderven, Lu Liu, Fernanda E. Ana-Sosa-Batiz, Thi H.O. Nguyen, Yanmin Wan, Bruce Wines, Phillip Mark Hogarth, Danielle Tilmanis, Arnold Reynaldi, Matthew S Parsons, Aeron C. Hurt, Miles Philip Davenport, Tom Kotsimbos, Allen Cheuk-Seng Cheng, Katherine Kedzierska, Xiaoyan Zhang, Jianqing Xu, Stephen Kent

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article numbere92750
Number of pages15
JournalJCI Insight
Volume2
Issue number13
DOIs
Publication statusPublished - 6 Jul 2017

Keywords

  • Immunology
  • Infectious disease

Cite this

Vanderven, H. A., Liu, L., Ana-Sosa-Batiz, F. E., Nguyen, T. H. O., Wan, Y., Wines, B., ... Kent, S. (2017). Fc functional antibodies in humans with severe H7N9 and seasonal influenza. JCI Insight, 2(13), [e92750]. https://doi.org/10.1172/jci.insight.92750
Vanderven, Hillary A. ; Liu, Lu ; Ana-Sosa-Batiz, Fernanda E. ; Nguyen, Thi H.O. ; Wan, Yanmin ; Wines, Bruce ; Hogarth, Phillip Mark ; Tilmanis, Danielle ; Reynaldi, Arnold ; Parsons, Matthew S ; Hurt, Aeron C. ; Davenport, Miles Philip ; Kotsimbos, Tom ; Cheng, Allen Cheuk-Seng ; Kedzierska, Katherine ; Zhang, Xiaoyan ; Xu, Jianqing ; Kent, Stephen. / Fc functional antibodies in humans with severe H7N9 and seasonal influenza. In: JCI Insight. 2017 ; Vol. 2, No. 13.
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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.",
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author = "Vanderven, {Hillary A.} and Lu Liu and Ana-Sosa-Batiz, {Fernanda E.} and Nguyen, {Thi H.O.} and Yanmin Wan and Bruce Wines and Hogarth, {Phillip Mark} and Danielle Tilmanis and Arnold Reynaldi and Parsons, {Matthew S} and Hurt, {Aeron C.} and Davenport, {Miles Philip} and Tom Kotsimbos and Cheng, {Allen Cheuk-Seng} and Katherine Kedzierska and Xiaoyan Zhang and Jianqing Xu and Stephen Kent",
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Vanderven, HA, Liu, L, Ana-Sosa-Batiz, FE, Nguyen, THO, Wan, Y, Wines, B, Hogarth, PM, Tilmanis, D, Reynaldi, A, Parsons, MS, Hurt, AC, Davenport, MP, Kotsimbos, T, Cheng, AC-S, Kedzierska, K, Zhang, X, Xu, J & Kent, S 2017, 'Fc functional antibodies in humans with severe H7N9 and seasonal influenza' JCI Insight, vol. 2, no. 13, e92750. https://doi.org/10.1172/jci.insight.92750

Fc functional antibodies in humans with severe H7N9 and seasonal influenza. / Vanderven, Hillary A.; Liu, Lu; Ana-Sosa-Batiz, Fernanda E.; Nguyen, Thi H.O. ; Wan, Yanmin; Wines, Bruce; Hogarth, Phillip Mark; Tilmanis, Danielle; Reynaldi, Arnold; Parsons, Matthew S; Hurt, Aeron C.; Davenport, Miles Philip; Kotsimbos, Tom; Cheng, Allen Cheuk-Seng; Kedzierska, Katherine; Zhang, Xiaoyan; Xu, Jianqing; Kent, Stephen.

In: JCI Insight, Vol. 2, No. 13, e92750, 06.07.2017.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Fc functional antibodies in humans with severe H7N9 and seasonal influenza

AU - Vanderven, Hillary A.

AU - Liu, Lu

AU - Ana-Sosa-Batiz, Fernanda E.

AU - Nguyen, Thi H.O.

AU - Wan, Yanmin

AU - Wines, Bruce

AU - Hogarth, Phillip Mark

AU - Tilmanis, Danielle

AU - Reynaldi, Arnold

AU - Parsons, Matthew S

AU - Hurt, Aeron C.

AU - Davenport, Miles Philip

AU - Kotsimbos, Tom

AU - Cheng, Allen Cheuk-Seng

AU - Kedzierska, Katherine

AU - Zhang, Xiaoyan

AU - Xu, Jianqing

AU - Kent, Stephen

PY - 2017/7/6

Y1 - 2017/7/6

N2 - 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.

AB - 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.

KW - Immunology

KW - Infectious disease

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U2 - 10.1172/jci.insight.92750

DO - 10.1172/jci.insight.92750

M3 - Article

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Vanderven HA, Liu L, Ana-Sosa-Batiz FE, Nguyen THO, Wan Y, Wines B et al. Fc functional antibodies in humans with severe H7N9 and seasonal influenza. JCI Insight. 2017 Jul 6;2(13). e92750. https://doi.org/10.1172/jci.insight.92750