Markers of Polyfunctional SARS-CoV-2 Antibodies in Convalescent Plasma.

Autor:	Natarajan H; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire, USA., Crowley AR; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire, USA., Butler SE; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire, USA., Xu S; Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA., Weiner JA; Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA., Bloch EM; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Littlefield K; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Wieland-Alter W; Department of Pediatrics, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA., Connor RI; Department of Pediatrics, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA., Wright PF; Department of Pediatrics, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA., Benner SE; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Bonny TS; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Laeyendecker O; Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Sullivan D; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.; Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Shoham S; Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Quinn TC; Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Larman HB; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Casadevall A; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.; Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Pekosz A; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Redd AD; Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA., Tobian AAR; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Ackerman ME; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire, USA margaret.e.ackerman@dartmouth.edu.; Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2021 Apr 20; Vol. 12 (2). Date of Electronic Publication: 2021 Apr 20.
DOI:	10.1128/mBio.00765-21
Abstrakt:	Convalescent plasma is a promising therapy for coronavirus disease 2019 (COVID-19), but the antibody characteristics that contribute to efficacy remain poorly understood. This study analyzed plasma samples from 126 eligible convalescent blood donors in addition to 15 naive individuals, as well as an additional 20 convalescent individuals as a validation cohort. Multiplexed Fc Array binding assays and functional antibody response assays were utilized to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody composition and activity. Donor convalescent plasma samples contained a range of antibody cell- and complement-mediated effector functions, indicating the diverse antiviral activity of humoral responses observed among recovered individuals. In addition to viral neutralization, convalescent plasma samples contained antibodies capable of mediating such Fc-dependent functions as complement activation, phagocytosis, and antibody-dependent cellular cytotoxicity against SARS-CoV-2. Plasma samples from a fraction of eligible donors exhibited high activity across all activities evaluated. These polyfunctional plasma samples could be identified with high accuracy with even single Fc Array features, whose correlation with polyfunctional activity was confirmed in the validation cohort. Collectively, these results expand understanding of the diversity of antibody-mediated antiviral functions associated with convalescent plasma, and the polyfunctional antiviral functions suggest that it could retain activity even when its neutralizing capacity is reduced by mutations in variant SARS-CoV-2. IMPORTANCE Convalescent plasma has been deployed globally as a treatment for COVID-19, but efficacy has been mixed. Better understanding of the antibody characteristics that may contribute to its antiviral effects is important for this intervention as well as offer insights into correlates of vaccine-mediated protection. Here, a survey of convalescent plasma activities, including antibody neutralization and diverse effector functions, was used to define plasma samples with broad activity profiles. These polyfunctional plasma samples could be reliably identified in multiple cohorts by multiplex assay, presenting a widely deployable screening test for plasma selection and investigation of vaccine-elicited responses. (Copyright © 2021 Natarajan et al.)
Databáze:	MEDLINE
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