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恒河猴中针对 SARS-CoV-2 的具有预防和治疗功效的中和抗体的鉴定。

Characterization of neutralizing antibody with prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus monkeys.

机构信息

Mabwell (Shanghai) Bioscience Co., Ltd, 201210, Shanghai, China.

Beijing Kohnoor Science & Technology Co., Ltd, 102206, Beijing, China.

出版信息

Nat Commun. 2020 Nov 13;11(1):5752. doi: 10.1038/s41467-020-19568-1.

DOI:10.1038/s41467-020-19568-1
PMID:33188207
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7666115/
Abstract

Efficacious interventions are urgently needed for the treatment of COVID-19. Here, we report a monoclonal antibody (mAb), MW05, with SARS-CoV-2 neutralizing activity by disrupting the interaction of receptor binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2) receptor. Crosslinking of Fc with FcγRIIB mediates antibody-dependent enhancement (ADE) activity by MW05. This activity is eliminated by introducing the LALA mutation to the Fc region (MW05/LALA). Potent prophylactic and therapeutic effects against SARS-CoV-2 are observed in rhesus monkeys. A single dose of MW05/LALA blocks infection of SARS-CoV-2 in prophylactic treatment and clears SARS-CoV-2 in three days in a therapeutic treatment setting. These results pave the way for the development of MW05/LALA as an antiviral strategy for COVID-19.

摘要

我们迫切需要有效的干预措施来治疗 COVID-19。在这里，我们报告了一种单克隆抗体 (mAb) MW05，它通过破坏受体结合域 (RBD) 与血管紧张素转化酶 2 (ACE2) 受体的相互作用具有 SARS-CoV-2 中和活性。Fc 与 FcγRIIB 的交联通过 MW05 介导抗体依赖性增强 (ADE) 活性。通过在 Fc 区引入 LALA 突变 (MW05/LALA) 可以消除这种活性。MW05/LALA 在恒河猴中表现出针对 SARS-CoV-2 的强大预防和治疗效果。MW05/LALA 的单次剂量可在预防治疗中阻断 SARS-CoV-2 的感染，并在治疗治疗中三天内清除 SARS-CoV-2。这些结果为开发 MW05/LALA 作为 COVID-19 的抗病毒策略铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae0/7666115/535e4fbd4ab3/41467_2020_19568_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae0/7666115/952dfc30ab38/41467_2020_19568_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae0/7666115/66b6f7292cf4/41467_2020_19568_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae0/7666115/49c5b55ec3a1/41467_2020_19568_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae0/7666115/535e4fbd4ab3/41467_2020_19568_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae0/7666115/952dfc30ab38/41467_2020_19568_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae0/7666115/66b6f7292cf4/41467_2020_19568_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae0/7666115/49c5b55ec3a1/41467_2020_19568_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae0/7666115/535e4fbd4ab3/41467_2020_19568_Fig4_HTML.jpg

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