A pathogen-like antigen-based vaccine confers immune protection against SARS-CoV-2 in non-human primates
Chang Ming Guo, Yanan Peng, Lin Lin, Xiaoyan Pan, Mengqi Fang, Yun Zhao, Keyan Bao, Runhan Li, Jian-Bao Han, Jiaorong Chen, Tian‐Zhang Song, Xiaoli Feng, Yahong Zhou, Gan Zhao, Leike Zhang, Yong‐Tang Zheng, Ping Zhu, Haiying Hang, Linqi Zhang, Zhaolin Hua, Hongyu Deng, Baidong Hou
Abstract
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 advantage of this natural pathway for vaccine development, synthetic pathogen-like antigens (PLAs) constructed of multivalent antigens with encapsulated TLR ligands can be used to activate B cell antigen receptors and TLRs in a synergistic manner. Here we report a PLA-based coronavirus disease 2019 (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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein as the target antigen. This PLA-based vaccine candidate induces robust neutralizing antibodies in both mice and non-human primates (NHPs). Using a NHP infection model, we demonstrate that the viral clearance is accelerated in vaccinated animals. In addition, the PLA-based vaccine induces a T helper 1 (Th1)-oriented response and a durable memory, supporting its potential for further clinical development.