Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies
Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies
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DOI：
10.1038/s41591-022-01792-5
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发表时间：
2022-03-23
期刊：
影响因子：
82.9
通讯作者：
Schwartz, Olivier
中科院分区：
文献类型：
--
作者：
Bruel, Timothee;Hadjadj, Jerome;Schwartz, Olivier
治疗性抗体和用治疗性抗体治疗的免疫功能低下个体的血清对SARS-CoV-2 Omicron BA.1和BA.2亚系的中和活性不同，这可能对暴露前和暴露后的治疗有影响。在许多国家，严重急性呼吸道综合征冠状病毒2 Omicron BA.1亚系已被BA.2亚系所取代。BA.2与BA.1的区别在于其刺突中的约21个突变。在这项研究中，我们首先比较了BA.1和BA.2对9种治疗性单克隆抗体（mAb）中和的敏感性。与BA.1不同，BA.2对cigavimab敏感，部分受imdevimab抑制，对adintrevimab和sotrovimab耐药。然后，我们分析了29名免疫功能低下个体在给予Ronapreve（casirivimab和imdevimab）和/或Evushold（cigavimab和tixagevimab）抗体混合物后长达1个月的血清。所有治疗的个体在其血清中显示出升高的抗体水平，这有效地中和了Delta变体。来自Ronapreve接受者的血清不中和BA.1并且弱抑制BA.2。BA.1和BA.2的中和分别在29个Evusheld受体中的19个和29个中检测到。与Delta变体相比，针对BA.1的中和滴度（344倍）比针对BA.2的中和滴度（9倍）更显著降低。我们进一步报告了29名患者中的4例突破性Omicron感染，表明抗体治疗不能完全预防感染。总的来说，BA.1和BA.2在它们对治疗性mAb的敏感性方面表现出明显的差异。在患者血清中，Ronapreve的抗Omicron中和活性降低，Evushold的中和活性降低程度较小。
Therapeutic antibodies, and sera from immunocompromised individuals prophylactically treated with therapeutic antibodies, differ in neutralizing activity against the SARS-CoV-2 Omicron BA.1 and BA.2 sublineages, which could have implications for pre-exposure and post-exposure treatment.The severe acute respiratory syndrome coronavirus 2 Omicron BA.1 sublineage has been supplanted in many countries by the BA.2 sublineage. BA.2 differs from BA.1 by about 21 mutations in its spike. In this study, we first compared the sensitivity of BA.1 and BA.2 to neutralization by nine therapeutic monoclonal antibodies (mAbs). In contrast to BA.1, BA.2 was sensitive to cilgavimab, partly inhibited by imdevimab and resistant to adintrevimab and sotrovimab. We then analyzed sera from 29 immunocompromised individuals up to 1 month after administration of Ronapreve (casirivimab and imdevimab) and/or Evusheld (cilgavimab and tixagevimab) antibody cocktails. All treated individuals displayed elevated antibody levels in their sera, which efficiently neutralized the Delta variant. Sera from Ronapreve recipients did not neutralize BA.1 and weakly inhibited BA.2. Neutralization of BA.1 and BA.2 was detected in 19 and 29 out of 29 Evusheld recipients, respectively. As compared to the Delta variant, neutralizing titers were more markedly decreased against BA.1 (344-fold) than BA.2 (nine-fold). We further report four breakthrough Omicron infections among the 29 individuals, indicating that antibody treatment did not fully prevent infection. Collectively, BA.1 and BA.2 exhibit noticeable differences in their sensitivity to therapeutic mAbs. Anti-Omicron neutralizing activity of Ronapreve and, to a lesser extent, that of Evusheld is reduced in patients' sera.