Decay of Fc-dependent antibody functions after mild to moderate COVID-19

Wen Shi Lee; Kevin John Selva; Samantha K. Davis; Bruce D. Wines; Arnold Reynaldi; Robyn Esterbauer; Hannah G. Kelly; Ebene R. Haycroft; Hyon Xhi Tan; Jennifer A. Juno; Adam K. Wheatley; P. Mark Hogarth; Deborah Cromer; Miles P. Davenport; Amy W. Chung; Stephen J. Kent

doi:10.1016/j.xcrm.2021.100296

Decay of Fc-dependent antibody functions after mild to moderate COVID-19

Wen Shi Lee, Kevin John Selva, Samantha K. Davis, Bruce D. Wines, Arnold Reynaldi, Robyn Esterbauer, Hannah G. Kelly, Ebene R. Haycroft, Hyon Xhi Tan, Jennifer A. Juno, Adam K. Wheatley, P. Mark Hogarth, Deborah Cromer, Miles P. Davenport, Amy W. Chung, Stephen J. Kent

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Abstract

The capacity of antibodies to engage with immune cells via the Fc region is important in preventing and controlling many infectious diseases. The evolution of such antibodies during convalescence from coronavirus disease 2019 (COVID-19) is largely unknown. We develop assays to measure Fc-dependent antibody functions against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-expressing cells in serial samples from subjects primarily with mild-moderate COVID-19 up to 149 days post-infection. We find that S-specific antibodies capable of engaging Fcγ receptors decay over time, with S-specific antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP) activity within plasma declining accordingly. Although there is significant decay in ADCC and ADP activity, they remain readily detectable in almost all subjects at the last time point studied (94%) in contrast with neutralization activity (70%). Although it remains unclear the degree to which Fc effector functions contribute to protection against SARS-CoV-2 re-infection, our results indicate that antibodies with Fc effector functions persist longer than neutralizing antibodies.

Original language	English
Article number	100296
Number of pages	15
Journal	Cell Reports Medicine
Volume	2
Issue number	6
DOIs	https://doi.org/10.1016/j.xcrm.2021.100296
Publication status	Published - 15 Jun 2021

Keywords

ADCC
ADP
antibody
convalescence
COVID-19
decay
Fc effector functions
phagocytosis
SARS-CoV-2
trogocytosis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.xcrm.2021.100296Licence: CC BY-NC-ND

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Lee, W. S., Selva, K. J., Davis, S. K., Wines, B. D., Reynaldi, A., Esterbauer, R., Kelly, H. G., Haycroft, E. R., Tan, H. X., Juno, J. A., Wheatley, A. K., Hogarth, P. M., Cromer, D., Davenport, M. P., Chung, A. W., & Kent, S. J. (2021). Decay of Fc-dependent antibody functions after mild to moderate COVID-19. Cell Reports Medicine, 2(6), Article 100296. https://doi.org/10.1016/j.xcrm.2021.100296

@article{dfbcfc89a58c4efcb131dd1eabcde258,

title = "Decay of Fc-dependent antibody functions after mild to moderate COVID-19",

abstract = "The capacity of antibodies to engage with immune cells via the Fc region is important in preventing and controlling many infectious diseases. The evolution of such antibodies during convalescence from coronavirus disease 2019 (COVID-19) is largely unknown. We develop assays to measure Fc-dependent antibody functions against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-expressing cells in serial samples from subjects primarily with mild-moderate COVID-19 up to 149 days post-infection. We find that S-specific antibodies capable of engaging Fcγ receptors decay over time, with S-specific antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP) activity within plasma declining accordingly. Although there is significant decay in ADCC and ADP activity, they remain readily detectable in almost all subjects at the last time point studied (94%) in contrast with neutralization activity (70%). Although it remains unclear the degree to which Fc effector functions contribute to protection against SARS-CoV-2 re-infection, our results indicate that antibodies with Fc effector functions persist longer than neutralizing antibodies.",

keywords = "ADCC, ADP, antibody, convalescence, COVID-19, decay, Fc effector functions, phagocytosis, SARS-CoV-2, trogocytosis",

author = "Lee, {Wen Shi} and Selva, {Kevin John} and Davis, {Samantha K.} and Wines, {Bruce D.} and Arnold Reynaldi and Robyn Esterbauer and Kelly, {Hannah G.} and Haycroft, {Ebene R.} and Tan, {Hyon Xhi} and Juno, {Jennifer A.} and Wheatley, {Adam K.} and Hogarth, {P. Mark} and Deborah Cromer and Davenport, {Miles P.} and Chung, {Amy W.} and Kent, {Stephen J.}",

note = "Funding Information: We thank the cohort participants for generously providing samples. We thank Francesca Mordant and Kanta Subbarao (University of Melbourne) for performing the SARS-CoV-2 neutralization assays. We acknowledge the Melbourne Cytometry Platform for provision of flow cytometry services. The following reagent was produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH: Spike glycoprotein receptor binding domain (RBD) from SARS-related coronavirus 2, Wuhan-Hu-1 with C-terminal histidine tag, recombinant from HEK293F cells, NR-52366. This study was supported by the Victorian Government , an Australian Government Medical Research Future Fund award GNT2002073 (S.J.K., M.P.D., and A.K.W.), the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology (S.J.K.), an NHMRC program grant APP1149990 (S.J.K. and M.P.D.), NHMRC project grants GNT1162760 (A.K.W.) and GNT1145303 (P.M.H. and B.D.W.), an NHMRC-EU collaborative award APP1115828 (S.J.K. and M.P.D.), the European Union Horizon 2020 Research and Innovation Programme under grant agreement 681137 (S.J.K.), and Emergent Ventures Fast Grants (A.W.C.). J.A.J., A.W.C., and S.J.K. are supported by NHMRC fellowships. A.K.W., D.C., and M.P.D. are supported by NHMRC Investigator grants. Figures were created using BioRender. Funding Information: We thank the cohort participants for generously providing samples. We thank Francesca Mordant and Kanta Subbarao (University of Melbourne) for performing the SARS-CoV-2 neutralization assays. We acknowledge the Melbourne Cytometry Platform for provision of flow cytometry services. The following reagent was produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH: Spike glycoprotein receptor binding domain (RBD) from SARS-related coronavirus 2, Wuhan-Hu-1 with C-terminal histidine tag, recombinant from HEK293F cells, NR-52366. This study was supported by the Victorian Government, an Australian Government Medical Research Future Fund award GNT2002073 (S.J.K. M.P.D. and A.K.W.), the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology (S.J.K.), an NHMRC program grant APP1149990 (S.J.K. and M.P.D.), NHMRC project grants GNT1162760 (A.K.W.) and GNT1145303 (P.M.H. and B.D.W.), an NHMRC-EU collaborative award APP1115828 (S.J.K. and M.P.D.), the European Union Horizon 2020 Research and Innovation Programme under grant agreement 681137 (S.J.K.), and Emergent Ventures Fast Grants (A.W.C.). J.A.J. A.W.C. and S.J.K. are supported by NHMRC fellowships. A.K.W. D.C. and M.P.D. are supported by NHMRC Investigator grants. Figures were created using BioRender. Conceptualization, W.S.L. A.K.W. M.P.D. A.W.C. and S.J.K.; methodology, W.S.L. K.J.S. S.K.D. and B.D.W.; formal analysis, W.S.L. K.J.S. S.K.D. B.D.W. A.R. D.C. M.P.D. and A.W.C.; investigation, W.S.L. K.J.S. S.K.D. B.D.W. E.R.H. and H.-X.T.; resources, R.E. H.G.K. J.A.J. and A.K.W.; writing ? original draft, W.S.L. and S.J.K.; writing ? review & editing, W.S.L. K.J.S. S.K.D. B.D.W. A.R. H.-X.T. J.A.J. A.K.W. P.M.H. D.C. M.P.D. A.W.C. and S.J.K.; supervision, A.K.W. A.W.C. and S.J.K.; funding acquisition, A.K.W. P.M.H. M.P.D. A.W.C. and S.J.K. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = jun,

day = "15",

doi = "10.1016/j.xcrm.2021.100296",

language = "English",

volume = "2",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Decay of Fc-dependent antibody functions after mild to moderate COVID-19

AU - Lee, Wen Shi

AU - Selva, Kevin John

AU - Davis, Samantha K.

AU - Wines, Bruce D.

AU - Reynaldi, Arnold

AU - Esterbauer, Robyn

AU - Kelly, Hannah G.

AU - Haycroft, Ebene R.

AU - Tan, Hyon Xhi

AU - Juno, Jennifer A.

AU - Wheatley, Adam K.

AU - Hogarth, P. Mark

AU - Cromer, Deborah

AU - Davenport, Miles P.

AU - Chung, Amy W.

AU - Kent, Stephen J.

N1 - Funding Information: We thank the cohort participants for generously providing samples. We thank Francesca Mordant and Kanta Subbarao (University of Melbourne) for performing the SARS-CoV-2 neutralization assays. We acknowledge the Melbourne Cytometry Platform for provision of flow cytometry services. The following reagent was produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH: Spike glycoprotein receptor binding domain (RBD) from SARS-related coronavirus 2, Wuhan-Hu-1 with C-terminal histidine tag, recombinant from HEK293F cells, NR-52366. This study was supported by the Victorian Government , an Australian Government Medical Research Future Fund award GNT2002073 (S.J.K., M.P.D., and A.K.W.), the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology (S.J.K.), an NHMRC program grant APP1149990 (S.J.K. and M.P.D.), NHMRC project grants GNT1162760 (A.K.W.) and GNT1145303 (P.M.H. and B.D.W.), an NHMRC-EU collaborative award APP1115828 (S.J.K. and M.P.D.), the European Union Horizon 2020 Research and Innovation Programme under grant agreement 681137 (S.J.K.), and Emergent Ventures Fast Grants (A.W.C.). J.A.J., A.W.C., and S.J.K. are supported by NHMRC fellowships. A.K.W., D.C., and M.P.D. are supported by NHMRC Investigator grants. Figures were created using BioRender. Funding Information: We thank the cohort participants for generously providing samples. We thank Francesca Mordant and Kanta Subbarao (University of Melbourne) for performing the SARS-CoV-2 neutralization assays. We acknowledge the Melbourne Cytometry Platform for provision of flow cytometry services. The following reagent was produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH: Spike glycoprotein receptor binding domain (RBD) from SARS-related coronavirus 2, Wuhan-Hu-1 with C-terminal histidine tag, recombinant from HEK293F cells, NR-52366. This study was supported by the Victorian Government, an Australian Government Medical Research Future Fund award GNT2002073 (S.J.K. M.P.D. and A.K.W.), the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology (S.J.K.), an NHMRC program grant APP1149990 (S.J.K. and M.P.D.), NHMRC project grants GNT1162760 (A.K.W.) and GNT1145303 (P.M.H. and B.D.W.), an NHMRC-EU collaborative award APP1115828 (S.J.K. and M.P.D.), the European Union Horizon 2020 Research and Innovation Programme under grant agreement 681137 (S.J.K.), and Emergent Ventures Fast Grants (A.W.C.). J.A.J. A.W.C. and S.J.K. are supported by NHMRC fellowships. A.K.W. D.C. and M.P.D. are supported by NHMRC Investigator grants. Figures were created using BioRender. Conceptualization, W.S.L. A.K.W. M.P.D. A.W.C. and S.J.K.; methodology, W.S.L. K.J.S. S.K.D. and B.D.W.; formal analysis, W.S.L. K.J.S. S.K.D. B.D.W. A.R. D.C. M.P.D. and A.W.C.; investigation, W.S.L. K.J.S. S.K.D. B.D.W. E.R.H. and H.-X.T.; resources, R.E. H.G.K. J.A.J. and A.K.W.; writing ? original draft, W.S.L. and S.J.K.; writing ? review & editing, W.S.L. K.J.S. S.K.D. B.D.W. A.R. H.-X.T. J.A.J. A.K.W. P.M.H. D.C. M.P.D. A.W.C. and S.J.K.; supervision, A.K.W. A.W.C. and S.J.K.; funding acquisition, A.K.W. P.M.H. M.P.D. A.W.C. and S.J.K. The authors declare no competing interests. Publisher Copyright: © 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/6/15

Y1 - 2021/6/15

N2 - The capacity of antibodies to engage with immune cells via the Fc region is important in preventing and controlling many infectious diseases. The evolution of such antibodies during convalescence from coronavirus disease 2019 (COVID-19) is largely unknown. We develop assays to measure Fc-dependent antibody functions against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-expressing cells in serial samples from subjects primarily with mild-moderate COVID-19 up to 149 days post-infection. We find that S-specific antibodies capable of engaging Fcγ receptors decay over time, with S-specific antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP) activity within plasma declining accordingly. Although there is significant decay in ADCC and ADP activity, they remain readily detectable in almost all subjects at the last time point studied (94%) in contrast with neutralization activity (70%). Although it remains unclear the degree to which Fc effector functions contribute to protection against SARS-CoV-2 re-infection, our results indicate that antibodies with Fc effector functions persist longer than neutralizing antibodies.

AB - The capacity of antibodies to engage with immune cells via the Fc region is important in preventing and controlling many infectious diseases. The evolution of such antibodies during convalescence from coronavirus disease 2019 (COVID-19) is largely unknown. We develop assays to measure Fc-dependent antibody functions against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-expressing cells in serial samples from subjects primarily with mild-moderate COVID-19 up to 149 days post-infection. We find that S-specific antibodies capable of engaging Fcγ receptors decay over time, with S-specific antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP) activity within plasma declining accordingly. Although there is significant decay in ADCC and ADP activity, they remain readily detectable in almost all subjects at the last time point studied (94%) in contrast with neutralization activity (70%). Although it remains unclear the degree to which Fc effector functions contribute to protection against SARS-CoV-2 re-infection, our results indicate that antibodies with Fc effector functions persist longer than neutralizing antibodies.

KW - ADCC

KW - ADP

KW - antibody

KW - convalescence

KW - COVID-19

KW - decay

KW - Fc effector functions

KW - phagocytosis

KW - SARS-CoV-2

KW - trogocytosis

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U2 - 10.1016/j.xcrm.2021.100296

DO - 10.1016/j.xcrm.2021.100296

M3 - Article

C2 - 33997824

AN - SCOPUS:85107696196

SN - 2666-3791

VL - 2

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 6

M1 - 100296

ER -

Decay of Fc-dependent antibody functions after mild to moderate COVID-19

Abstract

Keywords

UN SDGs

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ARC Centre of Excellence in Convergent Bio-Nano Science and Technology

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