A pathogen-like antigen based vaccine confers immune protection against SARS-CoV-2 in non-human primates

Guo, Chang; Peng, Yanan; Lin, Lin; Pan, Xiaoyan; Fang, Mengqi; Zhao, Yun; Bao, Keyan; Li, Runhan; Han, Jianbao; Chen, Jiaorong; Song, Tian-Zhang; Feng, Xiao-Li; Zhou, Yahong; Zhao, Gan; Zhang, Leike; Zheng, Yongtang; Zhu, Ping; Hang, Haiying; Zhang, Linqi; Hua, Zhaolin; Deng, Hongyu; Hou, Baidong

Activation of nucleic acid sensing Toll-like receptors (TLRs) in B cells is involved in antiviral responses by promoting B cell activation and germinal center responses. In order to take the advantage of this natural pathway for vaccine development, synthetic pathogen-like antigens (PLA) constructed of multivalent antigens with encapsulated TLR ligands can be used to to activate B cell antigen receptors and TLRs in a synergistic manner. Here we report a PLA-based COVID-19 vaccine candidate designed by combining a phage-derived virus-like particle carrying bacterial RNA as TLR ligands with the receptor-binding domain of SARS-CoV-2 S protein as the target antigen. This PLA-based vaccine candidate induced robust neutralizing antibodies in both mice and non-human primates (NHPs). Using a NHP infection model we demonstrated that the viral clearance was accelerated in vaccinated animals. In addition, the PLA-based vaccine induced Th1 oriented response and a durable memory, supporting its potential for further clinic development.