Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.
Texas Biomedical Research Institute, San Antonio, TX, USA.
Cell Rep Med. 2021 Mar 16;2(3):100218. doi: 10.1016/j.xcrm.2021.100218. Epub 2021 Feb 25.
SARS-CoV-2 infection results in viral burden in the respiratory tract, enabling transmission and leading to substantial lung pathology. The 1212C2 fully human monoclonal antibody was derived from an IgM memory B cell of a COVID-19 patient, has high affinity for the Spike protein receptor binding domain, neutralizes SARS-CoV-2, and exhibits prophylactic and therapeutic activity in hamsters when delivered intraperitoneally, reducing upper and lower respiratory viral burden and lung pathology. Inhalation of nebulized 1212C2 at levels as low as 0.6 mg/kg, corresponding to 0.03 mg/kg lung-deposited dose, reduced the viral burden below the detection limit and mitigated lung pathology. The therapeutic efficacy of an exceedingly low dose of inhaled 1212C2 supports the rationale for local lung delivery for dose-sparing benefits, as compared to the conventional parenteral route of administration. These results suggest that the clinical development of 1212C2 formulated and delivered via inhalation for the treatment of SARS-CoV-2 infection should be considered.
SARS-CoV-2 感染会导致呼吸道病毒载量增加，从而实现传播并导致严重的肺部病理变化。1212C2 是一种全人源单克隆抗体，源自一名 COVID-19 患者的 IgM 记忆 B 细胞，对 Spike 蛋白受体结合域具有高亲和力，可中和 SARS-CoV-2，在仓鼠中经腹腔给药时具有预防和治疗作用，可降低上呼吸道和下呼吸道的病毒载量并减轻肺部病理变化。以低至 0.6 毫克/千克的水平雾化吸入 1212C2，相当于肺沉积剂量 0.03 毫克/千克，可将病毒载量降低到检测限以下，并减轻肺部病理变化。吸入极低剂量的 1212C2 即可产生治疗效果，这支持了与传统的全身给药途径相比，通过局部肺部给药以节省剂量的原理。这些结果表明，应考虑开发 1212C2 并通过吸入给药用于治疗 SARS-CoV-2 感染。
