TY - JOUR
T1 - Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response
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.
AB - 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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U2 - 10.1038/s41467-021-27201-y
DO - 10.1038/s41467-021-27201-y
M3 - Article
C2 - 34824251
AN - SCOPUS:85119825037
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 6853
ER -