RBD-homodimer, a COVID-19 subunit vaccine candidate, elicits immunogenicity and protection in rodents and nonhuman primates

Xiaoyan Pan,Ge Gao,Shaohong Chen,Pengfei Zhou,Jing Shi ,Yun Peng,Jing Zhang,Cheng Peng,Lijuan Fang,Xue Hu,Xiliang Hu,Zhiming Yuan ,Yan Wu,Liang Zeng,Gong Chen ,Jiaxuan Zhao,Jizu Yi,Juhong Rao,Yanfeng Yao,Chao Shan,Hui Zhou,Yao Lu ,Yongxiang Yan,Kunpeng Liu,Wenjuan Cong,Xiaoxiao Gao,Weiwei Guo,Hui Xiong,Zili Wang,Weijuan Shang,Gengfu Xiao

doi:10.1038/s41421-021-00320-y

Abstract

The pandemic of COVID-19 caused by SARS-CoV-2 has raised a new challenges to the scientific and industrious fields after over 1-year spread across different countries. The ultimate approach to end the pandemic is the timely application of vaccines to achieve herd immunity. Here, a novel SARS-CoV-2 receptor-binding domain (RBD) homodimer was developed as a SARS-CoV-2 vaccine candidate. Formulated with aluminum adjuvant, RBD dimer elicited strong immune response in both rodents and non-human primates, and protected mice from SARS-CoV-2 challenge with significantly reducing viral load and alleviating pathological injury in the lung. In the non-human primates, the vaccine could prevent majority of the animals from SARS-CoV-2 infection in the respiratory tract and reduce lung damage. In addition, antibodies elicited by this vaccine candidate showed cross-neutralization activities to SARS-CoV-2 variants. Furthermore, with our expression system, we provided a high-yield RBD homodimer vaccine without additional biosafety or special transport device supports. Thus, it may serve as a safe, effective, and low-cost SARS-CoV-2 vaccine candidate.

Highlights

Introduction Up toJuly, 2021, the coronavirus disease 2019 (COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to over 189 million infections and more than 4.0 million deaths, with an average fatality rate of 2.1%
Through the analysis of S protein of SARS-CoV-2, a cysteine was identified at the C-terminus of receptor-binding domain (RBD), which might play a key role in the formation of stable dimers
With our previous experience of Fc fusion protein, the RBD and Fc fusion protein approach was taken to bring the C-terminal cysteines of the RBD protein closer, which increased the possibility of two RBD molecules forming disulfide bonds

Summary

Introduction

Introduction Up toJuly, 2021, the coronavirus disease 2019 (COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to over 189 million infections and more than 4.0 million deaths, with an average fatality rate of 2.1%. At the beginning of the outbreak, multiple forms of vaccines development were conducted worldwide, including inactivated vaccine, live attenuated vaccine, viral vector vaccine, nucleic acid vaccine, and protein subunit vaccine, etc. At least 26 vaccines have been approved for emergency use in several countries after or at phase III clinical trials[2], including the vaccines that have received high attention: inactivated vaccines by Sinopharm[3,4] and SINOVAC5, mRNA vaccines by BioNTech/Pfizer[6] and Moderna[7], adenovirus viral vector vaccines by AstraZeneca/University of Oxford[8] and CanSino[9], and protein subunit vaccine by Zhifei Longcom[10] and Novavax[11]. The yields of these vaccines are still too low to meet the

Methods

Results

Conclusion