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COVA1-18 中和抗体在三种临床前模型中预防 SARS-CoV-2。

COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models.

机构信息

Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France.

Departments of Medical Microbiology of the Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam, The Netherlands.

出版信息

Nat Commun. 2021 Oct 20;12(1):6097. doi: 10.1038/s41467-021-26354-0.

Abstract

Effective treatments against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Monoclonal antibodies have shown promising results in patients. Here, we evaluate the in vivo prophylactic and therapeutic effect of COVA1-18, a neutralizing antibody highly potent against the B.1.1.7 isolate. In both prophylactic and therapeutic settings, SARS-CoV-2 remains undetectable in the lungs of treated hACE2 mice. Therapeutic treatment also causes a reduction in viral loads in the lungs of Syrian hamsters. When administered at 10 mg kg-1 one day prior to a high dose SARS-CoV-2 challenge in cynomolgus macaques, COVA1-18 shows very strong antiviral activity in the upper respiratory compartments. Using a mathematical model, we estimate that COVA1-18 reduces viral infectivity by more than 95% in these compartments, preventing lymphopenia and extensive lung lesions. Our findings demonstrate that COVA1-18 has a strong antiviral activity in three preclinical models and could be a valuable candidate for further clinical evaluation.

摘要

急需针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的有效治疗方法。单克隆抗体已在患者中显示出良好的效果。在这里,我们评估了针对 B.1.1.7 分离株具有高中和活性的 COVA1-18 的体内预防和治疗效果。在预防和治疗环境中,治疗的 hACE2 小鼠肺部均无法检测到 SARS-CoV-2。治疗还导致叙利亚仓鼠肺部的病毒载量减少。当在感染高剂量 SARS-CoV-2 之前一天在食蟹猴中以 10 mg kg-1 给药时,COVA1-18 在呼吸道上部区域显示出很强的抗病毒活性。使用数学模型,我们估计 COVA1-18 在这些部位将病毒感染力降低了 95%以上,从而防止了淋巴细胞减少和广泛的肺部病变。我们的研究结果表明,COVA1-18 在三种临床前模型中具有很强的抗病毒活性,可能是进一步临床评估的有价值候选药物。

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