Transfusion Research Center, Belgian Red Cross-Flanders, Ghent, Belgium.
Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Sci Rep. 2024 Oct 9;14(1):23579. doi: 10.1038/s41598-024-75093-x.
We aimed to model binding of donor antibodies to virus that infects COVID-19 patients following transfusion of convalescent plasma (CCP). An immunosorbent assay was developed to determine apparent affinity (K). Antibody binding to virus was modelled using antibody concentration and estimations of viral load. Assay and model were validated using reference antibodies and clinical data of monoclonal antibody therapy. A single K or two resolvable K were found for IgG in 11% or 89% of CCP donations, respectively. For IgA this was 50%-50%. Median IgG K was 0.8nM and 3.6nM for IgA, ranging from 0.1-14.7nM and 0.2-156.0nM respectively. The median concentration of IgG was 44.0nM (range 8.4-269.0nM) and significantly higher than IgA at 2.0nM (range 0.4-11.4nM). The model suggested that a double CCP transfusion (i.e. 500 mL) allows for > 80% binding of antibody to virus provided K was < 1nM and concentration > 150nM. In our cohort from the pre-vaccination era, 4% of donations fulfilled these criteria. Low and mid-range viral loads are found early post exposure, suggesting that convalescent plasma will be most effective then. This study provides a biochemical rationale for selecting high affinity and high antibody concentration CCP transfused early in the disease course.
我们旨在建立模型，以预测在输注恢复期血浆（CCP）后，供体抗体与感染 COVID-19 患者的病毒的结合情况。开发了一种免疫吸附测定法来确定表观亲和力（K）。使用抗体浓度和病毒载量的估算值来模拟抗体与病毒的结合。使用参考抗体和单克隆抗体治疗的临床数据对测定法和模型进行了验证。在 11%或 89%的 CCP 捐赠物中，分别发现 IgG 有一个或两个可分辨的 K。对于 IgA，这一比例分别为 50%-50%。IgG 的中位数 K 为 0.8nM 和 3.6nM，而 IgA 的中位数 K 为 0.2-156.0nM。IgG 的中位数浓度为 44.0nM（范围为 8.4-269.0nM），明显高于 IgA 的浓度 2.0nM（范围为 0.4-11.4nM）。该模型表明，两次输注 CCP（即 500mL）可使抗体与病毒的结合率超过 80%，前提是 K<1nM 且浓度>150nM。在我们来自疫苗接种前时代的队列中，有 4%的捐赠物符合这些标准。在接触后早期发现低和中范围的病毒载量，这表明恢复期血浆在那时最有效。本研究为选择在疾病早期高亲和力和高抗体浓度的 CCP 输注提供了生化依据。
