In vitro antibody-mediated SARS-CoV-2 infection suppression through human ACE2 receptor blockade

IF 3.3 4区医学 Q3 IMMUNOLOGY

Immunology letters Pub Date : 2024-06-24 DOI:10.1016/j.imlet.2024.106887

Priscilla S. Redd , Alyssa D. Merting , John D. Klement , Dakota B. Poschel , Dafeng Yang , Kebin Liu

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引用次数: 0

Abstract

Vaccines and antibodies that specifically target or neutralize components of the SARS-CoV-2 virus are effective in prevention and treatment of human patients with SARS-CoV-2 infection. However, vaccines and SARS-CoV-2 neutralization antibodies target a subset of epitopes of viral proteins, and the fast evolution of the SARS-CoV-2 virus and the continuing emergence of SARS-CoV-2 variants confer SARS-CoV-2 immune escape from these therapies. ACE2 is the human cell receptor that serves as the entry point for SARS-CoV-2 into human cells and thus is the gatekeeper for SARS-CoV-2 infection of humans. We report here the development of 4G8C11, an anti-human ACE2 receptor monoclonal antibody that recognizes ACE2 on human cell surfaces. We determined that 4G8C11 blocks SARS-CoV-2 and variant infection of ACE2⁺ human cells. Furthermore, 4G8C11 has minimal effects on ACE2 receptor activity. 4G8C11 is therefore a monoclonal antibody for ACE2 receptor detection and potentially an effective immunotherapeutic agent for SARS-CoV-2 and variants.

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通过人类 ACE2 受体阻断体外抗体介导的 SARS-CoV-2 感染抑制。

专门针对或中和 SARS-CoV-2 病毒成分的疫苗和抗体可有效预防和治疗 SARS-CoV-2 感染者。然而，疫苗和 SARS-CoV-2 中和抗体只针对病毒蛋白的一部分表位，SARS-CoV-2 病毒的快速进化和 SARS-CoV-2 变异体的不断出现使 SARS-CoV-2 免疫逃逸于这些疗法之外。ACE2 是人体细胞受体，是 SARS-CoV-2 进入人体细胞的入口，因此也是 SARS-CoV-2 感染人类的守门员。我们在此报告抗人 ACE2 受体单克隆抗体 4G8C11 的开发情况，该抗体可识别人体细胞表面的 ACE2。我们确定 4G8C11 能阻止 SARS-CoV-2 和变体感染 ACE2+ 人体细胞。此外，4G8C11 对 ACE2 受体活性的影响极小。因此，4G8C11 是一种用于检测 ACE2 受体的单克隆抗体，有可能成为治疗 SARS-CoV-2 和变种的有效免疫治疗剂。

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来源期刊

Immunology letters 医学-免疫学

CiteScore

7.60

自引率

0.00%

发文量

审稿时长

44 days

期刊介绍： Immunology Letters provides a vehicle for the speedy publication of experimental papers, (mini)Reviews and Letters to the Editor addressing all aspects of molecular and cellular immunology. The essential criteria for publication will be clarity, experimental soundness and novelty. Results contradictory to current accepted thinking or ideas divergent from actual dogmas will be considered for publication provided that they are based on solid experimental findings. Preference will be given to papers of immediate importance to other investigators, either by their experimental data, new ideas or new methodology. Scientific correspondence to the Editor-in-Chief related to the published papers may also be accepted provided that they are short and scientifically relevant to the papers mentioned, in order to provide a continuing forum for discussion.