Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response

Jonathan D. Herman; Chuangqi Wang; Carolin Loos; Hyunah Yoon; Johanna Rivera; M. Eugenia Dieterle; Denise Haslwanter; Rohit K. Jangra; Robert H. Bortz; Katharine J. Bar; Boris Julg; Kartik Chandran; Douglas Lauffenburger; Liise anne Pirofski; Galit Alter

doi:10.1038/s41467-021-27201-y

Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response

Jonathan D. Herman, Chuangqi Wang, Carolin Loos, Hyunah Yoon, Johanna Rivera, M. Eugenia Dieterle, Denise Haslwanter, Rohit K. Jangra, Robert H. Bortz, Katharine J. Bar, Boris Julg, Kartik Chandran, Douglas Lauffenburger, Liise anne Pirofski, Galit Alter

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

2 Scopus citations

Abstract

Transfer of convalescent plasma (CP) had been proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have been mixed, potentially due to the heterogeneous nature of CP. Here we perform deep profiling of SARS-CoV-2-specific antibody titer, Fc-receptor binding, and Fc-mediated functional assays in CP units, as well as in plasma from hospitalized COVID-19 patients before and after CP administration. The profiling results show that, although all recipients exhibit expanded SARS-CoV-2-specific humoral immune responses, CP units contain more functional antibodies than recipient plasma. Meanwhile, CP functional profiles influence the evolution of recipient humoral immunity in conjuncture with the recipient’s pre-existing SARS-CoV2-specific antibody titers: CP-derived SARS-CoV-2 nucleocapsid-specific antibody functions are associated with muted humoral immune evolution in patients with high titer anti-spike IgG. Our data thus provide insights into the unexpected impact of CP-derived functional anti-spike and anti-nucleocapsid antibodies on the evolution of SARS-CoV-2-specific response following severe infection.

Original language	English (US)
Article number	6853
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-27201-y
State	Published - Dec 2021

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/s41467-021-27201-y

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Herman, J. D., Wang, C., Loos, C., Yoon, H., Rivera, J., Eugenia Dieterle, M., Haslwanter, D., Jangra, R. K., Bortz, R. H., Bar, K. J., Julg, B., Chandran, K., Lauffenburger, D., Pirofski, L. A., & Alter, G. (2021). Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response. Nature communications, 12(1), [6853]. https://doi.org/10.1038/s41467-021-27201-y

Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response. / Herman, Jonathan D.; Wang, Chuangqi; Loos, Carolin; Yoon, Hyunah ; Rivera, Johanna; Eugenia Dieterle, M.; Haslwanter, Denise; Jangra, Rohit K.; Bortz, Robert H.; Bar, Katharine J.; Julg, Boris; Chandran, Kartik; Lauffenburger, Douglas; Pirofski, Liise anne; Alter, Galit.

In: Nature communications, Vol. 12, No. 1, 6853, 12.2021.

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

Herman, JD, Wang, C, Loos, C, Yoon, H , Rivera, J, Eugenia Dieterle, M, Haslwanter, D, Jangra, RK, Bortz, RH, Bar, KJ, Julg, B, Chandran, K, Lauffenburger, D, Pirofski, LA & Alter, G 2021, 'Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response', Nature communications, vol. 12, no. 1, 6853. https://doi.org/10.1038/s41467-021-27201-y

Herman, Jonathan D. ; Wang, Chuangqi ; Loos, Carolin ; Yoon, Hyunah ; Rivera, Johanna ; Eugenia Dieterle, M. ; Haslwanter, Denise ; Jangra, Rohit K. ; Bortz, Robert H. ; Bar, Katharine J. ; Julg, Boris ; Chandran, Kartik ; Lauffenburger, Douglas ; Pirofski, Liise anne ; Alter, Galit. / Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response. In: Nature communications. 2021 ; Vol. 12, No. 1.

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title = "Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response",

abstract = "Transfer of convalescent plasma (CP) had been proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have been mixed, potentially due to the heterogeneous nature of CP. Here we perform deep profiling of SARS-CoV-2-specific antibody titer, Fc-receptor binding, and Fc-mediated functional assays in CP units, as well as in plasma from hospitalized COVID-19 patients before and after CP administration. The profiling results show that, although all recipients exhibit expanded SARS-CoV-2-specific humoral immune responses, CP units contain more functional antibodies than recipient plasma. Meanwhile, CP functional profiles influence the evolution of recipient humoral immunity in conjuncture with the recipient{\textquoteright}s pre-existing SARS-CoV2-specific antibody titers: CP-derived SARS-CoV-2 nucleocapsid-specific antibody functions are associated with muted humoral immune evolution in patients with high titer anti-spike IgG. Our data thus provide insights into the unexpected impact of CP-derived functional anti-spike and anti-nucleocapsid antibodies on the evolution of SARS-CoV-2-specific response following severe infection.",

author = "Herman, {Jonathan D.} and Chuangqi Wang and Carolin Loos and Hyunah Yoon and Johanna Rivera and {Eugenia Dieterle}, M. and Denise Haslwanter and Jangra, {Rohit K.} and Bortz, {Robert H.} and Bar, {Katharine J.} and Boris Julg and Kartik Chandran and Douglas Lauffenburger and Pirofski, {Liise anne} and Galit Alter",

note = "Funding Information: We thank Nancy Zimmerman, Mark, and Lisa Schwartz, an anonymous donor (financial support), Terry and Susan Ragon, and the SAMANA Kay MGH Research Scholars award for their support. We acknowledge support from the Ragon Institute of MGH, MIT, and Harvard, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the NIH (3R37AI080289-11S1, R01AI146785, R01-AI132633, R01-AI132633, U19AI42790-01, U19AI135995-02, U19AI42790-01, 1U01CA260476 – 01, CIVIC75N93019C00052, T32 AI007061, R01AI123654, R01AI143453, 3UL1TR002556-04S1), the G. Harold and Leila Y. Mathers Foundation, the Gates Foundation, the Global Health Vaccine Accelerator Platform funding (OPP1146996 and INV-001650), the Musk Foundation, and the Price Family Foundation. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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AU - Herman, Jonathan D.

AU - Wang, Chuangqi

AU - Loos, Carolin

AU - Yoon, Hyunah

AU - Rivera, Johanna

AU - Eugenia Dieterle, M.

AU - Haslwanter, Denise

AU - Jangra, Rohit K.

AU - Bortz, Robert H.

AU - Bar, Katharine J.

AU - Julg, Boris

AU - Chandran, Kartik

AU - Lauffenburger, Douglas

AU - Pirofski, Liise anne

AU - Alter, Galit

N1 - Funding Information: We thank Nancy Zimmerman, Mark, and Lisa Schwartz, an anonymous donor (financial support), Terry and Susan Ragon, and the SAMANA Kay MGH Research Scholars award for their support. We acknowledge support from the Ragon Institute of MGH, MIT, and Harvard, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the NIH (3R37AI080289-11S1, R01AI146785, R01-AI132633, R01-AI132633, U19AI42790-01, U19AI135995-02, U19AI42790-01, 1U01CA260476 – 01, CIVIC75N93019C00052, T32 AI007061, R01AI123654, R01AI143453, 3UL1TR002556-04S1), the G. Harold and Leila Y. Mathers Foundation, the Gates Foundation, the Global Health Vaccine Accelerator Platform funding (OPP1146996 and INV-001650), the Musk Foundation, and the Price Family Foundation. Publisher Copyright: © 2021, The Author(s).

PY - 2021/12

Y1 - 2021/12

N2 - Transfer of convalescent plasma (CP) had been proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have been mixed, potentially due to the heterogeneous nature of CP. Here we perform deep profiling of SARS-CoV-2-specific antibody titer, Fc-receptor binding, and Fc-mediated functional assays in CP units, as well as in plasma from hospitalized COVID-19 patients before and after CP administration. The profiling results show that, although all recipients exhibit expanded SARS-CoV-2-specific humoral immune responses, CP units contain more functional antibodies than recipient plasma. Meanwhile, CP functional profiles influence the evolution of recipient humoral immunity in conjuncture with the recipient’s pre-existing SARS-CoV2-specific antibody titers: CP-derived SARS-CoV-2 nucleocapsid-specific antibody functions are associated with muted humoral immune evolution in patients with high titer anti-spike IgG. Our data thus provide insights into the unexpected impact of CP-derived functional anti-spike and anti-nucleocapsid antibodies on the evolution of SARS-CoV-2-specific response following severe infection.

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Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response

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