Dynamics of antibodies to SARS-CoV-2 in convalescent plasma donors

Maurice Steenhuis; Gerard van Mierlo; Ninotska Il Derksen; Pleuni Ooijevaar-de Heer; Simone Kruithof; Floris L Loeff; Lea C Berkhout; Federica Linty; Chantal Reusken; Johan Reimerink; Boris Hogema; Hans Zaaijer; Leo van de Watering; Francis Swaneveld; Marit J van Gils; Berend Jan Bosch; S Marieke van Ham; Anja Ten Brinke; Gestur Vidarsson; Ellen C van der Schoot; Theo Rispens

doi:10.1002/cti2.1285

Dynamics of antibodies to SARS-CoV-2 in convalescent plasma donors

Maurice Steenhuis
, Gerard van Mierlo
, Ninotska Il Derksen
, Pleuni Ooijevaar-de Heer
, Simone Kruithof
, Floris L Loeff
, Lea C Berkhout
, Federica Linty
, Chantal Reusken
, Johan Reimerink
, Boris Hogema
, Hans Zaaijer
, Leo van de Watering
, Francis Swaneveld
, Marit J van Gils
, Berend Jan Bosch
, S Marieke van Ham
, Anja Ten Brinke
, Gestur Vidarsson
, Ellen C van der Schoot

Theo Rispens

Virology

Department of Immunopathology Sanquin Research Amsterdam The Netherlands
Department of Experimental Immunohematology Sanquin Research and Landsteiner Laboratory Amsterdam University Medical Centre Amsterdam The Netherlands
Department of Infectious Diseases Public Health Service region Utrecht Utrecht The Netherlands
Department of Virology Sanquin Diagnostic Services Amsterdam The Netherlands
Sanquin Blood Supply Foundation and Amsterdam University Medical Centre Amsterdam The Netherlands
Sanquin Blood Bank Unit Transfusion Medicine Leiden The Netherlands
Department of Transfusion Medicine Sanquin Blood Bank Amsterdam The Netherlands
Department of Medical Microbiology Amsterdam UMC University of Amsterdam Amsterdam The Netherlands

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Objectives: Characterisation of the human antibody response to SARS-CoV-2 infection is vital for serosurveillance purposes and for treatment options such as transfusion with convalescent plasma or immunoglobulin products derived from convalescent plasma. In this study, we longitudinally and quantitatively analysed antibody responses in RT-PCR-positive SARS-CoV-2 convalescent adults during the first 250 days after onset of symptoms.

Methods: We measured antibody responses to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the nucleocapsid protein in 844 longitudinal samples from 151 RT-PCR-positive SARS-CoV-2 convalescent adults. With a median of 5 (range 2-18) samples per individual, this allowed quantitative analysis of individual longitudinal antibody profiles. Kinetic profiles were analysed by mixed-effects modelling.

Results: All donors were seropositive at the first sampling moment, and only one donor seroreverted during follow-up analysis. Anti-RBD IgG and anti-nucleocapsid IgG levels declined with median half-lives of 62 and 59 days, respectively, 2-5 months after symptom onset, and several-fold variation in half-lives of individuals was observed. The rate of decline of antibody levels diminished during extended follow-up, which points towards long-term immunological memory. The magnitude of the anti-RBD IgG response correlated well with neutralisation capacity measured in a classic plaque reduction assay and in an in-house developed competitive assay.

Conclusion: The result of this study gives valuable insight into the long-term longitudinal response of antibodies to SARS-CoV-2.

Original language	English
Article number	e1285
Pages (from-to)	1-12
Journal	Clinical & translational immunology
Volume	10
Issue number	5
DOIs	https://doi.org/10.1002/cti2.1285
Publication status	Published - 2021

Bibliographical note

Funding Information:
We thank all the donors who have kindly donated plasma. This study was supported by the European Commission (SUPPORT‐E, grant number 101015756) and by ZonMW (Protective Immunity, grant number 10430 01 201 0012).

Publisher Copyright:
© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

Keywords

ACE2-competitive ELISA
COVID-19
antibodies
longitudinal
neutralisation

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cti2.1285Final published version, 805 KBLicence: CC BY

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Steenhuis, M., van Mierlo, G., Derksen, N. I., Ooijevaar-de Heer, P., Kruithof, S., Loeff, F. L., Berkhout, L. C., Linty, F., Reusken, C., Reimerink, J., Hogema, B., Zaaijer, H., van de Watering, L., Swaneveld, F., van Gils, M. J., Bosch, B. J., van Ham, S. M., Ten Brinke, A., Vidarsson, G., ... Rispens, T. (2021). Dynamics of antibodies to SARS-CoV-2 in convalescent plasma donors. Clinical & translational immunology, 10(5), 1-12. Article e1285. https://doi.org/10.1002/cti2.1285

@article{22aec6ac116f407dab7c751ee5786329,

title = "Dynamics of antibodies to SARS-CoV-2 in convalescent plasma donors",

abstract = "Objectives: Characterisation of the human antibody response to SARS-CoV-2 infection is vital for serosurveillance purposes and for treatment options such as transfusion with convalescent plasma or immunoglobulin products derived from convalescent plasma. In this study, we longitudinally and quantitatively analysed antibody responses in RT-PCR-positive SARS-CoV-2 convalescent adults during the first 250 days after onset of symptoms.Methods: We measured antibody responses to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the nucleocapsid protein in 844 longitudinal samples from 151 RT-PCR-positive SARS-CoV-2 convalescent adults. With a median of 5 (range 2-18) samples per individual, this allowed quantitative analysis of individual longitudinal antibody profiles. Kinetic profiles were analysed by mixed-effects modelling.Results: All donors were seropositive at the first sampling moment, and only one donor seroreverted during follow-up analysis. Anti-RBD IgG and anti-nucleocapsid IgG levels declined with median half-lives of 62 and 59 days, respectively, 2-5 months after symptom onset, and several-fold variation in half-lives of individuals was observed. The rate of decline of antibody levels diminished during extended follow-up, which points towards long-term immunological memory. The magnitude of the anti-RBD IgG response correlated well with neutralisation capacity measured in a classic plaque reduction assay and in an in-house developed competitive assay.Conclusion: The result of this study gives valuable insight into the long-term longitudinal response of antibodies to SARS-CoV-2.",

keywords = "ACE2-competitive ELISA, COVID-19, antibodies, longitudinal, neutralisation",

author = "Maurice Steenhuis and \{van Mierlo\}, Gerard and Derksen, \{Ninotska Il\} and \{Ooijevaar-de Heer\}, Pleuni and Simone Kruithof and Loeff, \{Floris L\} and Berkhout, \{Lea C\} and Federica Linty and Chantal Reusken and Johan Reimerink and Boris Hogema and Hans Zaaijer and \{van de Watering\}, Leo and Francis Swaneveld and \{van Gils\}, \{Marit J\} and Bosch, \{Berend Jan\} and \{van Ham\}, \{S Marieke\} and \{Ten Brinke\}, Anja and Gestur Vidarsson and \{van der Schoot\}, \{Ellen C\} and Theo Rispens",

note = "Funding Information: We thank all the donors who have kindly donated plasma. This study was supported by the European Commission (SUPPORT‐E, grant number 101015756) and by ZonMW (Protective Immunity, grant number 10430 01 201 0012). Publisher Copyright: {\textcopyright} 2021 The Authors. Clinical \& Translational Immunology published by John Wiley \& Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.",

year = "2021",

doi = "10.1002/cti2.1285",

language = "English",

volume = "10",

pages = "1--12",

journal = "Clinical \& translational immunology",

issn = "2050-0068",

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Steenhuis, M, van Mierlo, G, Derksen, NI, Ooijevaar-de Heer, P, Kruithof, S, Loeff, FL, Berkhout, LC, Linty, F, Reusken, C, Reimerink, J, Hogema, B, Zaaijer, H, van de Watering, L, Swaneveld, F, van Gils, MJ, Bosch, BJ, van Ham, SM, Ten Brinke, A, Vidarsson, G, van der Schoot, EC & Rispens, T 2021, 'Dynamics of antibodies to SARS-CoV-2 in convalescent plasma donors', Clinical & translational immunology, vol. 10, no. 5, e1285, pp. 1-12. https://doi.org/10.1002/cti2.1285

TY - JOUR

T1 - Dynamics of antibodies to SARS-CoV-2 in convalescent plasma donors

AU - Steenhuis, Maurice

AU - van Mierlo, Gerard

AU - Derksen, Ninotska Il

AU - Ooijevaar-de Heer, Pleuni

AU - Kruithof, Simone

AU - Loeff, Floris L

AU - Berkhout, Lea C

AU - Linty, Federica

AU - Reusken, Chantal

AU - Reimerink, Johan

AU - Hogema, Boris

AU - Zaaijer, Hans

AU - van de Watering, Leo

AU - Swaneveld, Francis

AU - van Gils, Marit J

AU - Bosch, Berend Jan

AU - van Ham, S Marieke

AU - Ten Brinke, Anja

AU - Vidarsson, Gestur

AU - van der Schoot, Ellen C

AU - Rispens, Theo

N1 - Funding Information: We thank all the donors who have kindly donated plasma. This study was supported by the European Commission (SUPPORT‐E, grant number 101015756) and by ZonMW (Protective Immunity, grant number 10430 01 201 0012). Publisher Copyright: © 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

PY - 2021

Y1 - 2021

N2 - Objectives: Characterisation of the human antibody response to SARS-CoV-2 infection is vital for serosurveillance purposes and for treatment options such as transfusion with convalescent plasma or immunoglobulin products derived from convalescent plasma. In this study, we longitudinally and quantitatively analysed antibody responses in RT-PCR-positive SARS-CoV-2 convalescent adults during the first 250 days after onset of symptoms.Methods: We measured antibody responses to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the nucleocapsid protein in 844 longitudinal samples from 151 RT-PCR-positive SARS-CoV-2 convalescent adults. With a median of 5 (range 2-18) samples per individual, this allowed quantitative analysis of individual longitudinal antibody profiles. Kinetic profiles were analysed by mixed-effects modelling.Results: All donors were seropositive at the first sampling moment, and only one donor seroreverted during follow-up analysis. Anti-RBD IgG and anti-nucleocapsid IgG levels declined with median half-lives of 62 and 59 days, respectively, 2-5 months after symptom onset, and several-fold variation in half-lives of individuals was observed. The rate of decline of antibody levels diminished during extended follow-up, which points towards long-term immunological memory. The magnitude of the anti-RBD IgG response correlated well with neutralisation capacity measured in a classic plaque reduction assay and in an in-house developed competitive assay.Conclusion: The result of this study gives valuable insight into the long-term longitudinal response of antibodies to SARS-CoV-2.

AB - Objectives: Characterisation of the human antibody response to SARS-CoV-2 infection is vital for serosurveillance purposes and for treatment options such as transfusion with convalescent plasma or immunoglobulin products derived from convalescent plasma. In this study, we longitudinally and quantitatively analysed antibody responses in RT-PCR-positive SARS-CoV-2 convalescent adults during the first 250 days after onset of symptoms.Methods: We measured antibody responses to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the nucleocapsid protein in 844 longitudinal samples from 151 RT-PCR-positive SARS-CoV-2 convalescent adults. With a median of 5 (range 2-18) samples per individual, this allowed quantitative analysis of individual longitudinal antibody profiles. Kinetic profiles were analysed by mixed-effects modelling.Results: All donors were seropositive at the first sampling moment, and only one donor seroreverted during follow-up analysis. Anti-RBD IgG and anti-nucleocapsid IgG levels declined with median half-lives of 62 and 59 days, respectively, 2-5 months after symptom onset, and several-fold variation in half-lives of individuals was observed. The rate of decline of antibody levels diminished during extended follow-up, which points towards long-term immunological memory. The magnitude of the anti-RBD IgG response correlated well with neutralisation capacity measured in a classic plaque reduction assay and in an in-house developed competitive assay.Conclusion: The result of this study gives valuable insight into the long-term longitudinal response of antibodies to SARS-CoV-2.

KW - ACE2-competitive ELISA

KW - COVID-19

KW - antibodies

KW - longitudinal

KW - neutralisation

UR - https://www.scopus.com/pages/publications/85106885458

U2 - 10.1002/cti2.1285

DO - 10.1002/cti2.1285

M3 - Article

C2 - 34026115

SN - 2050-0068

VL - 10

SP - 1

EP - 12

JO - Clinical & translational immunology

JF - Clinical & translational immunology

IS - 5

M1 - e1285

ER -

Dynamics of antibodies to SARS-CoV-2 in convalescent plasma donors

Abstract

Bibliographical note

Keywords

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