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Characterisation of antibody dependent cellular phagocytosis in patients infected with Hepatitis C virus with different clinical outcomes
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  • Anurag Adhikari,
  • Arunasingam Abayasingam,
  • Nicholas Brasher A,
  • Ha Na Kim,
  • Megan Lord,
  • David Agapiou,
  • Lisa Maher,
  • Chaturaka Rodrigo,
  • Andrew Lloyd,
  • Rowena Bull,
  • Nicodemus Tedla
Anurag Adhikari
The University of Sydney School of Medical Sciences
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Arunasingam Abayasingam
The University of Sydney School of Medical Sciences
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Nicholas Brasher A
The University of Sydney School of Medical Sciences
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Ha Na Kim
UNSW Sydney
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Megan Lord
UNSW Sydney
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David Agapiou
The Kirby Institute
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Lisa Maher
The Kirby Institute
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Chaturaka Rodrigo
The University of Sydney School of Medical Sciences
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Andrew Lloyd
The University of Sydney School of Medical Sciences
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Rowena Bull
The University of Sydney School of Medical Sciences
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Nicodemus Tedla
The University of Sydney School of Medical Sciences

Corresponding Author:[email protected]

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Abstract

Early neutralising antibodies against Hepatitis C virus (HCV) and CD8+T cell effector responses can lead to viral clearance. However, these functions alone are not sufficient to protect patients against HCV infection, thus yet undefined additional anti-viral immune mechanisms are required. In recent years, Fc-receptor-dependent antibody effector functions particularly, antibody-dependent cellular phagocytosis (ADCP) was shown to offer immune protection against several RNA viruses. However, its development, and clinical role in patients with HCV infection remain unknown. In this study, we found that patients with chronic GT1a or GT3a HCV infection had significantly higher concentrations of anti-envelop 2 (E2) antibodies, predominantly IgG1 subclass, than patients that cleared the viruses while the latter had antibodies with higher affinities. 97% of the patients with HCV had measurable ADCP of whom patients with chronic disease showed significantly higher ADCP than those who naturally cleared the virus. Epitope mapping studies showed that patients with antibodies that target antigenic domains on the HCV E2 protein that are known to associate with neutralisation function also strongly associated with ADCP, suggesting antibodies with overlapping/dual functions. Correlation studies showed that ADCP significantly correlated with plasma anti-E2 antibody levels and neutralisation function regardless of clinical outcome and genotype of infecting virus while a significant correlation between ADCP and affinity was only evident in patients that cleared the virus. These results suggest ADCP was mostly driven by antibody titre in patients with chronic disease while maintained in clearers due the quality (affinity) of their anti-E2 antibodies despite having lower antibody titres.
21 Jul 2023Submitted to Journal of Medical Virology
21 Jul 2023Submission Checks Completed
21 Jul 2023Assigned to Editor
21 Jul 2023Review(s) Completed, Editorial Evaluation Pending
27 Jul 2023Reviewer(s) Assigned
18 Aug 2023Editorial Decision: Revise Major