Background Although coronavirus disease 2019 (COVID-19) vaccinations have provided a significant reduction in infections, effective COVID-19 treatments remain an urgent need. Methods Functional characterization of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hyperimmune immunoglobulin (hIG) from human convalescent plasma was performed by different virus neutralization methodologies (plaque reduction, virus-induced cytotoxicity, median tissue culture infectious dose [TCID50] reduction, and immunofluorimetry) at different laboratories using geographically different SARS-CoV-2 isolates (USA [1], Italy [1], and Spain [2]; 2 containing the D614G mutation). Neutralization capacity against the original Wuhan SARS-CoV-2 strain and variants (D614G mutant, B.1.1.7, P.1, and B.1.351) was evaluated using a pseudovirus expressing the corresponding spike (S) protein. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) was also evaluated. Results All SARS-CoV-2 isolates were potently neutralized by hIG as shown by all 4 methodologies. Wild-type SARS-CoV-2 and variants were effectively neutralized using the pseudovirus. The hIG (IgG type) induced ADCC and ADCP against SARS-CoV-2 N and S proteins but not E protein. Very low concentrations (25–100 µg IgG/mL) were required. A potent effect was triggered by antibodies in hIG solutions against the SARS-CoV-2 S and N proteins. Conclusions Beyond neutralization, IgG Fc-dependent pathways may play a role in combatting SARS-CoV-2 infections using COVID-19 hIG. This could be especially relevant for the treatment of more neutralization-resistant SARS-CoV-2 variants.

中文翻译：

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抗严重急性呼吸综合征冠状病毒 2 超免疫免疫球蛋白通过 N 和 S 蛋白表现出有效的中和和抗体依赖性细胞毒性和吞噬作用

背景 尽管 2019 年冠状病毒病 (COVID-19) 疫苗接种已显着减少感染，但有效的 COVID-19 治疗仍然是迫切需要的。方法 通过不同的病毒中和方法（斑块减少、病毒诱导的细胞毒性、中值组织培养感染剂量 [ TCID50] 减少和免疫荧光测定）在不同实验室使用地理上不同的 SARS-CoV-2 分离株（美国 [1]、意大利 [1] 和西班牙 [2]；2 包含 D614G 突变）。对原始武汉 SARS-CoV-2 毒株和变体（D614G 突变体、B.1.1.7、P.1 和 B.1）的中和能力。351) 使用表达相应刺突 (S) 蛋白的假病毒进行了评估。还评估了抗体依赖性细胞毒性 (ADCC) 和抗体依赖性细胞吞噬作用 (ADCP)。结果 如所有 4 种方法所示，所有 SARS-CoV-2 分离株均被 hIG 有效中和。野生型 SARS-CoV-2 及其变体被假病毒有效中和。hIG（IgG 型）诱导针对 SARS-CoV-2 N 和 S 蛋白而非 E 蛋白的 ADCC 和 ADCP。需要非常低的浓度（25–100 µg IgG/mL）。hIG 溶液中针对 SARS-CoV-2 S 和 N 蛋白的抗体触发了有效的作用。结论 除了中和作用之外，IgG Fc 依赖性途径可能在使用 COVID-19 hIG 对抗 SARS-CoV-2 感染中发挥作用。