Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire, USA.
Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA.
mBio. 2021 Apr 20;12(2):e00765-21. doi: 10.1128/mBio.00765-21.
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. 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.
恢复期血浆是治疗 2019 年冠状病毒病（COVID-19）的一种很有前途的疗法，但对有助于疗效的抗体特征仍了解甚少。本研究分析了 126 名符合条件的恢复期献血者的血浆样本，以及 15 名未感染个体和另外 20 名恢复期个体的验证队列。利用多重 Fc 阵列结合分析和功能性抗体反应分析来评估严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）抗体组成和活性。供体恢复期血浆样本含有一系列抗体细胞和补体介导的效应功能，表明在恢复个体中观察到的体液反应具有不同的抗病毒活性。除了病毒中和作用外，恢复期血浆样本还含有能够介导补体激活、吞噬作用和抗体依赖的细胞毒性等 Fc 依赖性功能的抗体，以对抗 SARS-CoV-2。在评估的所有功能中，有一部分合格供体的血浆样本表现出高活性。即使使用单个 Fc 阵列特征，也可以非常准确地识别出这些多功能血浆样本，并且在验证队列中证实了其与多功能活性的相关性。总的来说，这些结果扩展了对与恢复期血浆相关的抗体介导抗病毒功能多样性的理解，并且这些多功能抗病毒功能表明，即使在 SARS-CoV-2 变异导致其中和能力降低的情况下，它仍可能保持活性。恢复期血浆已在全球范围内用于治疗 COVID-19，但疗效不一。更好地了解可能有助于其抗病毒作用的抗体特征对于这种干预措施以及对疫苗介导保护的相关性研究都很重要。在这里，通过调查恢复期血浆的多种活性，包括抗体中和作用和多种效应功能，定义了具有广泛活性谱的血浆样本。这些多功能血浆样本可以通过多重分析在多个队列中可靠地识别，这为血浆选择和疫苗诱导反应的研究提供了一种广泛应用的筛选测试。
