Grifols Bioscience Industrial Group, Research Triangle Park, North Carolina, USA.
Transfusion. 2021 Jun;61(6):1705-1709. doi: 10.1111/trf.16378. Epub 2021 Mar 22.
In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus emerged in China and quickly spread into a worldwide pandemic. Prior to the development of specific drug therapies or a vaccine, more immediately available treatments were sought including convalescent plasma. A potential improvement from convalescent plasma could be the preparation of anti-SARS-CoV-2 hyperimmune globulin (hIVIG).
Convalescent plasma was collected from an existing network of plasma donation centers. A caprylate/chromatography purification process was used to manufacture hIVIG. Initial batches of hIVIG were manufactured in a versatile, small-scale facility designed and built to rapidly address emerging infectious diseases.
Processing convalescent plasma into hIVIG resulted in a highly purified immunoglobulin G (IgG) product with more concentrated neutralizing antibody activity. hIVIG will allow for the administration of greater antibody activity per unit of volume with decreased potential for several adverse events associated with plasma administration. IgG concentration and IgG specific to SARS-CoV-2 were increased over 10-fold from convalescent plasma to the final product. Normalized enzyme-linked immunosorbent assay activity (per mg/ml IgG) was maintained throughout the process. Protein content in these final product batches was 100% IgG, consisting of 98% monomer and dimer forms. Potentially hazardous proteins (IgM, IgA, and anti-A, anti-B, and anti-D) were reduced to minimal levels.
Multiple batches of anti-SARS-CoV-2 hIVIG that met regulatory requirements were manufactured from human convalescent plasma. The first clinical study in which the hIVIG will be evaluated will be Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC) [NCT04546581].
2019 年末，严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）病毒在中国出现，并迅速蔓延成为全球大流行。在开发出特定的药物疗法或疫苗之前，人们寻求更直接的治疗方法，包括恢复期血浆。恢复期血浆的一种潜在改进方法是制备抗 SARS-CoV-2 高免疫球蛋白（hIVIG）。
从现有的血浆捐赠中心网络中采集恢复期血浆。采用辛酸/层析纯化工艺制备 hIVIG。最初的 hIVIG 批次是在一个灵活的、小规模的设施中制造的，该设施旨在快速应对新发传染病。
将恢复期血浆加工成 hIVIG 可得到高度纯化的免疫球蛋白 G（IgG）产品，其中含有更浓缩的中和抗体活性。hIVIG 将允许每单位体积给予更高的抗体活性，同时降低与血浆给予相关的几种不良反应的风险。hIVIG 中的 IgG 浓度和针对 SARS-CoV-2 的 IgG 比恢复期血浆中的浓度分别增加了 10 多倍。在整个过程中，标准化酶联免疫吸附试验活性（每毫克/毫升 IgG）得以维持。这些最终产品批次的蛋白质含量为 100% IgG，由 98%的单体和二聚体形式组成。潜在危险蛋白（IgM、IgA 和抗-A、抗-B 和抗-D）减少到最低水平。
从人类恢复期血浆中制造了多批符合监管要求的抗 SARS-CoV-2 hIVIG。将对 hIVIG 进行评估的首个临床研究是“住院患者冠状病毒免疫球蛋白治疗（ITAC）”[NCT04546581]。
