Institut Pasteur, Université Paris Cité, CNRS UMR3569, Virus and Immunity Unit, Paris, France.
Vaccine Research Institute, Créteil, France.
Nat Med. 2022 Jun;28(6):1297-1302. doi: 10.1038/s41591-022-01792-5. Epub 2022 Mar 23.
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.
严重急性呼吸综合征冠状病毒 2 奥密克戎 BA.1 亚谱系已在许多国家被 BA.2 亚谱系取代。BA.2 在其刺突蛋白中与 BA.1 大约有 21 个突变不同。在这项研究中,我们首先比较了 BA.1 和 BA.2 对九种治疗性单克隆抗体(mAb)中和的敏感性。与 BA.1 不同,BA.2 对 cilgavimab 敏感,部分被 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接受 Ronapreve(casirivimab 和 imdevimab)和/或 Evusheld(cilgavimab 和 tixagevimab)抗体鸡尾酒治疗后 1 个月内的血清。所有接受治疗的个体的血清中均显示出升高的抗体水平,这些抗体可有效中和 Delta 变异株。Ronapreve 受者的血清不能中和 BA.1,只能微弱抑制 BA.2。在 29 名 Evusheld 受者中分别检测到 19 名和 29 名中和 BA.1 和 BA.2。与 Delta 变异株相比,针对 BA.1 的中和滴度下降更为显著(344 倍),而对 BA.2 的下降幅度较小(9 倍)。我们进一步报告了 29 名个体中的 4 例突破性奥密克戎感染,表明抗体治疗并未完全预防感染。综上所述,BA.1 和 BA.2 在对治疗性 mAb 的敏感性方面表现出明显差异。Ronapreve 和 Evusheld 的抗奥密克戎中和活性在患者血清中降低,Evusheld 的降低程度较小。