Endogenous Antibody Responses to SARS-CoV-2 in Patients With Mild or Moderate COVID-19 Who Received Bamlanivimab Alone or Bamlanivimab and Etesevimab Together.
Endogenous Antibody Responses to SARS-CoV-2 in Patients With Mild or Moderate COVID-19 Who Received Bamlanivimab Alone or Bamlanivimab and Etesevimab Together.
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DOI：
10.3389/fimmu.2021.790469
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发表时间：
2021
影响因子：
7.3
通讯作者：
Benschop RJ
中科院分区：
文献类型：
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作者：
Zhang L;Poorbaugh J;Dougan M;Chen P;Gottlieb RL;Huhn G;Beasley S;Daniels M;Ngoc Vy Trinh T;Crisp M;Freitas JJ;Vaillancourt P;Patel DR;Nirula A;Kallewaard NL;Higgs RE;Benschop RJ
SARS-CoV-2的中和性单克隆抗体（mAb）在早期给药时具有临床有效性，可降低轻度或中度COVID-19患者的住院率和死亡率。我们研究了SARS-CoV-2感染后接受mAb（单独的bamlanivimab和bamlanivimab和etesevimab一起）对内源性免疫应答的影响。在BLAZE-1试验中，从轻度或中度COVID-19患者中收集纵向血清样本，这些患者接受安慰剂（n=153）、单独使用bamlanivimab [700 mg（n=100）、2800 mg（n=106）或7000 mg（n=98）]或bamlanivimab（2800 mg）和etesevimab（2800 mg）联合治疗（n=111）。多重Luminex血清学测定测量针对SARS-CoV-2抗原的抗体滴度，包括逃避bamlanivimab或etesevimab结合的SARS-CoV-2蛋白变体，并进行SARS-CoV-2假病毒中和测定。接受安慰剂或mAb的患者的抗体应答具有广泛的特异性。在第15-85天，mAb接受者中针对受体结合结构域突变体（Spike-RBD E484 Q）以及N-末端结构域（Spike-NTD）和核衣壳蛋白（NCP）表位的滴度较基线的变化比安慰剂低1.4至4.1倍。与安慰剂相比，来自bamlanivimab单药治疗队列的第29天血清对加标E484 Q和β变体（B.1.351）的中和活性略微降低（分别降低3.1倍，p=0.001和2.9倍，p=0.002）。早期病毒载量与天然、未修饰体液应答的后续抗体滴度相关（对于全长加标，在第15、29、60和85天p<0.0001）。接受mAb治疗的轻度或中度COVID-19患者对SARS-CoV-2产生了广泛的抗原反应。滴度和中和活性的小幅降低（可能是由于mAb处理后病毒载量降低所致）表明mAb处理对内源性免疫应答的影响极小。
Neutralizing monoclonal antibodies (mAbs) to SARS-CoV-2 are clinically efficacious when administered early, decreasing hospitalization and mortality in patients with mild or moderate COVID-19. We investigated the effects of receiving mAbs (bamlanivimab alone and bamlanivimab and etesevimab together) after SARS-CoV-2 infection on the endogenous immune response. Longitudinal serum samples were collected from patients with mild or moderate COVID-19 in the BLAZE-1 trial who received placebo (n=153), bamlanivimab alone [700 mg (n=100), 2800 mg (n=106), or 7000 mg (n=98)], or bamlanivimab (2800 mg) and etesevimab (2800 mg) together (n=111). A multiplex Luminex serology assay measured antibody titers against SARS-CoV-2 antigens, including SARS-CoV-2 protein variants that evade bamlanivimab or etesevimab binding, and SARS-CoV-2 pseudovirus neutralization assays were performed. The antibody response in patients who received placebo or mAbs had a broad specificity. Titer change from baseline against a receptor-binding domain mutant (Spike-RBD E484Q), as well as N-terminal domain (Spike-NTD) and nucleocapsid protein (NCP) epitopes were 1.4 to 4.1 fold lower at day 15-85 in mAb recipients compared with placebo. Neutralizing activity of day 29 sera from bamlanivimab monotherapy cohorts against both spike E484Q and beta variant (B.1.351) were slightly reduced compared with placebo (by a factor of 3.1, p=0.001, and 2.9, p=0.002, respectively). Early viral load correlated with the subsequent antibody titers of the native, unmodified humoral response (p<0.0001 at Day 15, 29, 60 and 85 for full-length spike). Patients with mild or moderate COVID-19 treated with mAbs develop a wide breadth of antigenic responses to SARS-CoV-2. Small reductions in titers and neutralizing activity, potentially due to a decrease in viral load following mAb treatment, suggest minimal impact of mAb treatment on the endogenous immune response.