Identification of Novel Neutralizing Monoclonal Antibodies against SARS-CoV-2 Spike Glycoprotein,ACS Pharmacology & Translational Science

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Identification of Novel Neutralizing Monoclonal Antibodies against SARS-CoV-2 Spike Glycoprotein
ACS Pharmacology & Translational Science ( IF 4.9 ) Pub Date : 2021-07-29 , DOI: 10.1021/acsptsci.1c00058
Devivasha Bordoloi ₁ , Ziyang Xu ₁ , Michelle Ho ₁ , Mansi Purwar ₁ , Pratik Bhojnagarwala ₁ , Joel Cassel ₂ , Leila B Giron ₁ , Susanne Walker ₁ , Abhijeet J Kulkarni ₁ , Edgar Tello Ruiz ₁ , Jihae Choi ₁ , Faraz I Zaidi ₁ , Yuanhan Wu ₁ , Shaoying Wang ₃ , Ami Patel ₁ , Stephanie Ramos ₄ , Trevor Smith ₄ , Daniel Kulp ₁ , Kenneth E Ugen ₅ , Alagarsamy Srinivasan ₆ , Mohamed Abdel-Mohsen ₁ , Laurent Humeau ₄ , David B Weiner ₁ , Kar Muthumani ₁

Affiliation

Coronavirus disease 2019 (COVID-19) is caused by the newly emerged human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the highly contagious nature of SARS-CoV-2, it has infected more than 137 million individuals and caused more than 2.9 million deaths globally as of April 13, 2021. There is an urgent need to develop effective novel therapeutic strategies to treat or prevent this infection. Toward this goal, we focused on the development of monoclonal antibodies (mAbs) directed against the SARS-CoV-2 spike glycoprotein (SARS-CoV-2 Spike) present on the surface of virus particles as well as virus-infected cells. We isolated anti-SARS-CoV-2 Spike mAbs from animals immunized with a DNA vaccine. We then selected a highly potent set of mAbs against SARS-CoV-2 Spike protein and evaluated each candidate for their expression, target binding affinity, and neutralization potential using complementary ACE2-blocking and pseudovirus neutralization assays. We identified a total of 10 antibodies, which specifically and strongly bound to SARS-CoV-2 Spike, blocked the receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) interaction, and neutralized SARS-CoV-2. Furthermore, the glycomic profile of the antibodies suggested that they have high Fc-mediated effector functions. These antibodies should be further investigated for elucidating the neutralizing epitopes on Spike for the design of next-generation vaccines and for their potential in diagnostic as well as therapeutic utilities against SARS-CoV-2.

中文翻译：

抗 SARS-CoV-2 刺突糖蛋白的新型中和单克隆抗体的鉴定

2019 年冠状病毒病 (COVID-19) 是由新出现的人类冠状病毒、严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 引起的。由于 SARS-CoV-2 的高度传染性，截至 2021 年 4 月 13 日，它已感染全球超过 1.37 亿人，并导致超过 290 万人死亡。迫切需要开发有效的新型治疗策略来治疗或治疗预防这种感染。为了实现这一目标，我们专注于开发针对病毒颗粒以及病毒感染细胞表面的 SARS-CoV-2 刺突糖蛋白 (SARS-CoV-2 Spike) 的单克隆抗体 (mAb)。我们从接受 DNA 疫苗免疫的动物中分离出了抗 SARS-CoV-2 Spike mAb。然后，我们选择了一组针对 SARS-CoV-2 Spike 蛋白的高效单克隆抗体，并使用互补的 ACE2 阻断和假病毒中和测定评估了每种候选药物的表达、靶点结合亲和力和中和潜力。我们总共鉴定了 10 种抗体，它们与 SARS-CoV-2 Spike 特异性且强烈结合，阻断受体结合域 (RBD) 和血管紧张素转换酶 2 (ACE2) 相互作用，并中和 SARS-CoV-2。此外，抗体的糖组谱表明它们具有高 Fc 介导的效应功能。应进一步研究这些抗体，以阐明 Spike 上的中和表位，以设计下一代疫苗及其在针对 SARS-CoV-2 的诊断和治疗用途中的潜力。

更新日期：2021-08-13

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