Seasonal coronavirus-specific B cells with limited SARS-CoV-2 cross-reactivity dominate the IgG response in severe COVID-19

Muriel Aguilar-Bretones; Brenda M. Westerhuis; Matthijs P. Raadsen; Erwin de Bruin; Felicity D. Chandler; Nisreen M.A. Okba; Bart L. Haagmans; Thomas Langerak; Henrik Endeman; Johannes P.C. van den Akker; Diederik A.M.P.J. Gommers; Eric C.M. van Gorp; Corine H. GeurtsvanKessel; Rory D. de Vries; Ron A.M. Fouchier; Barry H.G. Rockx; Marion P.G. Koopmans; Gijsbert P. van Nierop

doi:10.1172/JCI150613

Seasonal coronavirus-specific B cells with limited SARS-CoV-2 cross-reactivity dominate the IgG response in severe COVID-19

^*Corresponding author for this work

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19). Little is known about the interplay between preexisting immunity to endemic seasonal coronaviruses and the development of a SARS-CoV-2–specific IgG response. We investigated the kinetics, breadth, magnitude, and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal and epidemic coronaviruses at the clonal level in patients with mild or severe COVID-19 as well as in disease control patients. We assessed antibody reactivity to nucleocapsid and spike antigens and correlated this IgG response to SARS-CoV-2 neutralization. Patients with COVID-19 mounted a mostly type-specific SARS-CoV-2 response. Additionally, IgG clones directed against a seasonal coronavirus were boosted in patients with severe COVID-19. These boosted clones showed limited cross-reactivity and did not neutralize SARS-CoV-2. These findings indicate a boost of poorly protective CoV-specific antibodies in patients with COVID-19 that correlated with disease severity, revealing “original antigenic sin.”

Original language	English
Article number	e150613
Number of pages	14
Journal	Journal of Clinical Investigation
Volume	131
Issue number	21
DOIs	https://doi.org/10.1172/JCI150613
Publication status	Published - 1 Nov 2021

Bibliographical note

Acknowledgments:
This study was funded by the European Union’s Horizon 2020
research and innovation program under grant agreements
from the Versatile Emerging Infectious Disease Observatory (VEO; 874735), Rapid European COVID-19 Emergency
Response Research (RECoVER; 101003589), and the Netherlands Organization for Health Research and Development (ZonMw; 10150062010008). We acknowledge Berend Jan Bosch,
Chunyan Wang, and Wentao Li (Utrecht University, Netherlands) for generously supplying the SECTO antigens; Katharina S.
Schmitz for technical assistance with the biosafety level 3 work;
and Georges M.G.M. Verjans and Pieter L.A. Fraaij for scientific
discussions (EMC, Rotterdam, Netherlands).

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Aguilar-Bretones, M., Westerhuis, B. M., Raadsen, M. P., de Bruin, E., Chandler, F. D., Okba, N. M. A., Haagmans, B. L., Langerak, T., Endeman, H., van den Akker, J. P. C., Gommers, D. A. M. P. J., van Gorp, E. C. M., GeurtsvanKessel, C. H., de Vries, R. D., Fouchier, R. A. M., Rockx, B. H. G., Koopmans, M. P. G., & van Nierop, G. P. (2021). Seasonal coronavirus-specific B cells with limited SARS-CoV-2 cross-reactivity dominate the IgG response in severe COVID-19. Journal of Clinical Investigation, 131(21), Article e150613. https://doi.org/10.1172/JCI150613

@article{1f0f80ad2bc94ec7a40f0e8737e2720f,

title = "Seasonal coronavirus-specific B cells with limited SARS-CoV-2 cross-reactivity dominate the IgG response in severe COVID-19",

abstract = "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19). Little is known about the interplay between preexisting immunity to endemic seasonal coronaviruses and the development of a SARS-CoV-2–specific IgG response. We investigated the kinetics, breadth, magnitude, and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal and epidemic coronaviruses at the clonal level in patients with mild or severe COVID-19 as well as in disease control patients. We assessed antibody reactivity to nucleocapsid and spike antigens and correlated this IgG response to SARS-CoV-2 neutralization. Patients with COVID-19 mounted a mostly type-specific SARS-CoV-2 response. Additionally, IgG clones directed against a seasonal coronavirus were boosted in patients with severe COVID-19. These boosted clones showed limited cross-reactivity and did not neutralize SARS-CoV-2. These findings indicate a boost of poorly protective CoV-specific antibodies in patients with COVID-19 that correlated with disease severity, revealing “original antigenic sin.”",

author = "Muriel Aguilar-Bretones and Westerhuis, \{Brenda M.\} and Raadsen, \{Matthijs P.\} and \{de Bruin\}, Erwin and Chandler, \{Felicity D.\} and Okba, \{Nisreen M.A.\} and Haagmans, \{Bart L.\} and Thomas Langerak and Henrik Endeman and \{van den Akker\}, \{Johannes P.C.\} and Gommers, \{Diederik A.M.P.J.\} and \{van Gorp\}, \{Eric C.M.\} and GeurtsvanKessel, \{Corine H.\} and \{de Vries\}, \{Rory D.\} and Fouchier, \{Ron A.M.\} and Rockx, \{Barry H.G.\} and Koopmans, \{Marion P.G.\} and \{van Nierop\}, \{Gijsbert P.\}",

note = "Acknowledgments: This study was funded by the European Union{\textquoteright}s Horizon 2020 research and innovation program under grant agreements from the Versatile Emerging Infectious Disease Observatory (VEO; 874735), Rapid European COVID-19 Emergency Response Research (RECoVER; 101003589), and the Netherlands Organization for Health Research and Development (ZonMw; 10150062010008). We acknowledge Berend Jan Bosch, Chunyan Wang, and Wentao Li (Utrecht University, Netherlands) for generously supplying the SECTO antigens; Katharina S. Schmitz for technical assistance with the biosafety level 3 work; and Georges M.G.M. Verjans and Pieter L.A. Fraaij for scientific discussions (EMC, Rotterdam, Netherlands).",

year = "2021",

month = nov,

day = "1",

doi = "10.1172/JCI150613",

language = "English",

volume = "131",

journal = "Journal of Clinical Investigation",

issn = "0021-9738",

publisher = "American Society for Clinical Investigation",

number = "21",

}

Aguilar-Bretones, M, Westerhuis, BM, Raadsen, MP, de Bruin, E, Chandler, FD, Okba, NMA, Haagmans, BL, Langerak, T, Endeman, H , van den Akker, JPC , Gommers, DAMPJ , van Gorp, ECM , GeurtsvanKessel, CH , de Vries, RD , Fouchier, RAM, Rockx, BHG, Koopmans, MPG & van Nierop, GP 2021, 'Seasonal coronavirus-specific B cells with limited SARS-CoV-2 cross-reactivity dominate the IgG response in severe COVID-19', Journal of Clinical Investigation, vol. 131, no. 21, e150613. https://doi.org/10.1172/JCI150613

TY - JOUR

T1 - Seasonal coronavirus-specific B cells with limited SARS-CoV-2 cross-reactivity dominate the IgG response in severe COVID-19

AU - Aguilar-Bretones, Muriel

AU - Westerhuis, Brenda M.

AU - Raadsen, Matthijs P.

AU - de Bruin, Erwin

AU - Chandler, Felicity D.

AU - Okba, Nisreen M.A.

AU - Haagmans, Bart L.

AU - Langerak, Thomas

AU - Endeman, Henrik

AU - van den Akker, Johannes P.C.

AU - Gommers, Diederik A.M.P.J.

AU - van Gorp, Eric C.M.

AU - GeurtsvanKessel, Corine H.

AU - de Vries, Rory D.

AU - Fouchier, Ron A.M.

AU - Rockx, Barry H.G.

AU - Koopmans, Marion P.G.

AU - van Nierop, Gijsbert P.

N1 - Acknowledgments: This study was funded by the European Union’s Horizon 2020 research and innovation program under grant agreements from the Versatile Emerging Infectious Disease Observatory (VEO; 874735), Rapid European COVID-19 Emergency Response Research (RECoVER; 101003589), and the Netherlands Organization for Health Research and Development (ZonMw; 10150062010008). We acknowledge Berend Jan Bosch, Chunyan Wang, and Wentao Li (Utrecht University, Netherlands) for generously supplying the SECTO antigens; Katharina S. Schmitz for technical assistance with the biosafety level 3 work; and Georges M.G.M. Verjans and Pieter L.A. Fraaij for scientific discussions (EMC, Rotterdam, Netherlands).

PY - 2021/11/1

Y1 - 2021/11/1

N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19). Little is known about the interplay between preexisting immunity to endemic seasonal coronaviruses and the development of a SARS-CoV-2–specific IgG response. We investigated the kinetics, breadth, magnitude, and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal and epidemic coronaviruses at the clonal level in patients with mild or severe COVID-19 as well as in disease control patients. We assessed antibody reactivity to nucleocapsid and spike antigens and correlated this IgG response to SARS-CoV-2 neutralization. Patients with COVID-19 mounted a mostly type-specific SARS-CoV-2 response. Additionally, IgG clones directed against a seasonal coronavirus were boosted in patients with severe COVID-19. These boosted clones showed limited cross-reactivity and did not neutralize SARS-CoV-2. These findings indicate a boost of poorly protective CoV-specific antibodies in patients with COVID-19 that correlated with disease severity, revealing “original antigenic sin.”

AB - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19). Little is known about the interplay between preexisting immunity to endemic seasonal coronaviruses and the development of a SARS-CoV-2–specific IgG response. We investigated the kinetics, breadth, magnitude, and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal and epidemic coronaviruses at the clonal level in patients with mild or severe COVID-19 as well as in disease control patients. We assessed antibody reactivity to nucleocapsid and spike antigens and correlated this IgG response to SARS-CoV-2 neutralization. Patients with COVID-19 mounted a mostly type-specific SARS-CoV-2 response. Additionally, IgG clones directed against a seasonal coronavirus were boosted in patients with severe COVID-19. These boosted clones showed limited cross-reactivity and did not neutralize SARS-CoV-2. These findings indicate a boost of poorly protective CoV-specific antibodies in patients with COVID-19 that correlated with disease severity, revealing “original antigenic sin.”

UR - https://www.scopus.com/pages/publications/85118495434

U2 - 10.1172/JCI150613

DO - 10.1172/JCI150613

M3 - Article

C2 - 34499051

AN - SCOPUS:85118495434

SN - 0021-9738

VL - 131

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

IS - 21

M1 - e150613

ER -

Seasonal coronavirus-specific B cells with limited SARS-CoV-2 cross-reactivity dominate the IgG response in severe COVID-19

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