Despite the success of SARS-CoV-2 vaccines, there remains a need for more prevention and treatment options for individuals remaining at risk of COVID-19. Monoclonal antibodies (mAbs) against the viral spike protein have potential to both prevent and treat COVID-19, and reduce the risk of severe disease and death. Here, we describe AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct non-overlapping epitopes on the spike protein receptor binding domain to potently neutralize SARS-CoV-2. Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and abrogate effector functions. The AZD7442 mAbs individually prevent the spike protein from binding to angiotensin-converting enzyme 2 receptor, blocking virus cell entry. Together, these two mAbs create a higher barrier to viral escape and a wider breadth of coverage, neutralizing all known SARS-CoV-2 variants of concern. In a non-human primate model of SARS-CoV-2 infection, prophylactic AZD7442 administration prevented infection, while therapeutic administration accelerated virus clearance from lung. In an ongoing Phase I study in healthy participants (NCT04507256), 300 mg intramuscular AZD7442 provided SARS-CoV-2 serum geometric mean neutralizing titers >10-fold above those of convalescent sera for >=3 months, which remained 3-fold above those of convalescent sera 9 months post-AZD7442 administration. Approximately 1-2% of serum AZD7442 levels were detected in nasal mucosa, a site of SARS-CoV-2 infection. Extrapolation of the time course of serum AZD7442 concentrations suggests AZD7442 may provide up to 12 months of protection and benefit individuals at high-risk of COVID-19.

中文翻译：

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AZD7442 在非人类灵长类动物中表现出预防和治疗功效，并延长了人类的半衰期

尽管 SARS-CoV-2 疫苗取得了成功，但仍然需要为仍处于 COVID-19 风险中的个人提供更多的预防和治疗选择。针对病毒刺突蛋白的单克隆抗体 (mAb) 具有预防和治疗 COVID-19 并降低严重疾病和死亡风险的潜力。在这里，我们描述了 AZD7442，这是两种 mAb 的组合，AZD8895（tixagevimab）和 AZD1061（cilgavimab），它们同时与刺突蛋白受体结合域上不同的非重叠表位结合，以有效中和 SARS-CoV-2。这两种单克隆抗体最初是从先前感染过 SARS-CoV-2 的个体中分离出来的，旨在延长其半衰期并消除效应子功能。AZD7442 mAb 单独阻止刺突蛋白与血管紧张素转换酶 2 受体结合，从而阻止病毒细胞进入。这两种 mAb 共同为病毒逃逸创造了更高的障碍和更广泛的覆盖范围，中和了所有已知的 SARS-CoV-2 相关变体。在 SARS-CoV-2 感染的非人类灵长类动物模型中，预防性给药 AZD7442 可预防感染，而治疗性给药可加速病毒从肺中的清除。在一项对健康参与者进行的 I 期研究 (NCT04507256) 中，300 毫克肌肉注射 AZD7442 提供的 SARS-CoV-2 血清几何平均中和滴度是恢复期血清的几何平均中和滴度 >=3 个月，是恢复期血清的 10 倍以上，仍然是恢复期血清的 3 倍AZD7442 给药后 9 个月的恢复期血清。在 SARS-CoV-2 感染部位鼻粘膜中检测到大约 1-2% 的血清 AZD7442 水平。