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. ABSTRACT 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.
【저자키워드】 COVID-19, convalescent plasma, SARS-CoV-2, IgG, antibody, neutralization, IgA, functional antibody response, ADCC, phagocytosis, 【초록키워드】 coronavirus disease, convalescent plasma, Coronavirus disease 2019, Efficacy, coronavirus, therapy, Mutation, Antiviral, antibody, Antibody Response, variant, Intervention, complement, antiviral activity, severe acute respiratory syndrome Coronavirus, Antiviral effect, Complement activation, activity, Blood donors, Viral, Humoral response, Characteristics, Features, plasma, phagocytosis, neutralizing capacity, humoral responses, viral neutralization, respiratory, convalescent, correlation, function, antibody-dependent cellular cytotoxicity, Donor, binding, Diversity, blood donor, acute respiratory syndrome, Activation, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, plasma samples, fraction, validation cohort, functions, high accuracy, offer, convalescent plasma samples, Cell, plasma sample, convalescent individual, analyzed, evaluate, addition, evaluated, reduced, exhibited, functional, contribute, individuals, Better, expand, eligible, treatment for COVID-19,