Evaluation of SARS-CoV-2-Neutralizing Nanobody Using Virus Receptor Binding Domain-Administered Model Mice

Song Liu; Guanghui Li; Lei Ding; Jin Ding; Qian Zhang; Dan Li; Xingguo Hou; Xiangxing Kong; Jing Zou; Shiming Zhang; Hongbin Han; Yakun Wan; Zhi Yang; Hua Zhu

doi:10.34133/2022/9864089

Evaluation of SARS-CoV-2-Neutralizing Nanobody Using Virus Receptor Binding Domain-Administered Model Mice

Research (Wash D C). 2022 Jul 22:2022:9864089. doi: 10.34133/2022/9864089. eCollection 2022.

Authors

Song Liu^{1

2}, Guanghui Li³, Lei Ding⁴, Jin Ding¹, Qian Zhang¹, Dan Li¹, Xingguo Hou¹, Xiangxing Kong¹, Jing Zou^{5

6}, Shiming Zhang^{5

6}, Hongbin Han^{5

6

7}, Yakun Wan³, Zhi Yang^{1

2

5}, Hua Zhu^{1

2

5}

Affiliations

¹ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China.
² Institute of Biomedical Engineering, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, China.
³ Shanghai Novamab Biopharmaceuticals Co., Ltd., Shanghai, China.
⁴ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Anesthesiology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
⁵ Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China.
⁶ Beijing Key Laboratory of Magnetic Resonance Imaging Devices and Technology, Peking University Third Hospital, Beijing 100191, China.
⁷ Department of Radiology, Peking University Third Hospital, Peking University, Beijing 100191, China.

Abstract

Due to the rapid spread of coronavirus disease 2019 (COVID-19), there is an urgent requirement for the development of additional diagnostic tools for further analysis of the disease. The isolated nanobody Nb11-59 binds to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) with high affinity to neutralize the virus and block the angiotensin-converting enzyme 2- (ACE2-) RBD interaction. Here, we introduce a novel nanobody-based radiotracer named ⁶⁸Ga-Nb1159. The radiotracer retained high affinity for the RBD and showed reliable radiochemical characteristics both in vitro and in vivo. Preclinical positron emission tomography (PET) studies of ⁶⁸Ga-Nb1159 in mice revealed its rapid clearance from circulation and robust uptake into the renal and urinary systems. Fortunately, ⁶⁸Ga-Nb1159 could specifically reveal the distribution of the RBD in mice. This study also helped to evaluate the pharmacodynamic effects of the neutralizing nanobody. Moreover, ⁶⁸Ga-Nb1159 may be a promising tool to explore the distribution of the RBD and improve the understanding of the virus. In particular, this study identified a novel molecular radioagent and established a reliable evaluation method for specifically investigating the RBD through noninvasive and visual PET technology.