Biomedical Translation Research Center (BioTReC), Academia Sinica, Taipei, 11529, Taiwan.
Institute of Cellular and Organismic Biology, Academia Sinica, No. 128, Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan.
J Biomed Sci. 2021 Nov 23;28(1):80. doi: 10.1186/s12929-021-00777-9.
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus with a high mutation rate. Importantly, several currently circulating SARS-CoV-2 variants are associated with loss of efficacy for both vaccines and neutralizing antibodies.
We analyzed the binding activity of six highly potent antibodies to the spike proteins of SARS-CoV-2 variants, assessed their neutralizing abilities with pseudovirus and authentic SARS-CoV-2 variants and evaluate efficacy of antibody cocktail in Delta SARS-CoV-2-infected hamster models as prophylactic and post-infection treatments.
The tested RBD-chAbs, except RBD-chAb-25, maintained binding ability to spike proteins from SARS-CoV-2 variants. However, only RBD-chAb-45 and -51 retained neutralizing activities; RBD-chAb-1, -15, -25 and -28 exhibited diminished neutralization for all SARS-CoV-2 variants. Notably, several cocktails of our antibodies showed low IC values (3.35-27.06 ng/ml) against the SARS-CoV-2 variant pseudoviruses including United Kingdom variant B.1.1.7 (Alpha), South Africa variant B.1.351 (Beta), Brazil variant P1 (Gamma), California variant B.1.429 (Epsilon), New York variant B.1.526 (Iota), and India variants, B.1.617.1 (Kappa) and B.1.617.2 (Delta). RBD-chAb-45, and -51 showed PRNT values 4.93-37.54 ng/ml when used as single treatments or in combination with RBD-chAb-15 or -28, according to plaque assays with authentic Alpha, Gamma and Delta SARS-CoV-2 variants. Furthermore, the antibody cocktail of RBD-chAb-15 and -45 exhibited potent prophylactic and therapeutic effects in Delta SARS-CoV-2 variant-infected hamsters.
The cocktail of RBD-chAbs exhibited potent neutralizing activities against SARS-CoV-2 variants. These antibody cocktails are highly promising candidate tools for controlling new SARS-CoV-2 variants, including Delta.
由高突变率的 RNA 病毒严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起的 2019 年冠状病毒病（COVID-19）。重要的是，目前流行的几种 SARS-CoV-2 变体与疫苗和中和抗体的效力丧失有关。
我们分析了六种强效抗体对 SARS-CoV-2 变体刺突蛋白的结合活性，评估了它们对假病毒和真实 SARS-CoV-2 变体的中和能力，并评估了抗体鸡尾酒在 Delta SARS-CoV-2 感染的仓鼠模型中作为预防和感染后治疗的效果。
测试的 RBD-chAb，除 RBD-chAb-25 外，均保持对 SARS-CoV-2 变体刺突蛋白的结合能力。然而，只有 RBD-chAb-45 和 -51 保留了中和活性；RBD-chAb-1、-15、-25 和 -28 对所有 SARS-CoV-2 变体的中和活性均减弱。值得注意的是，我们的几种抗体鸡尾酒对包括英国变体 B.1.1.7（Alpha）、南非变体 B.1.351（Beta）、巴西变体 P1（Gamma）、加利福尼亚变体 B.1.429（Epsilon）、纽约变体 B.1.526（Iota）和印度变体 B.1.617.1（Kappa）和 B.1.617.2（Delta）的 SARS-CoV-2 变体假病毒具有低 IC 值（3.35-27.06 ng/ml）。当用作单一治疗或与 RBD-chAb-15 或 -28 联合使用时，RBD-chAb-45 和 -51 在针对真实的 Alpha、Gamma 和 Delta SARS-CoV-2 变体的噬菌斑测定中显示出 4.93-37.54 ng/ml 的 PRNT 值。此外，RBD-chAb-15 和 -45 的抗体鸡尾酒在 Delta SARS-CoV-2 变体感染的仓鼠中表现出强大的预防和治疗效果。
RBD-chAb 的鸡尾酒对 SARS-CoV-2 变体表现出强大的中和活性。这些抗体鸡尾酒是控制包括 Delta 在内的新型 SARS-CoV-2 变体的极具前景的候选工具。
