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

作者：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 · 发表于：Cell Reports Medicine · 年份：2021 · DOI：10.1016/j.xcrm.2021.100448 · 被引用次数：18 · 研究领域：SARS-CoV-2 and COVID-19 Research、Immunotherapy and Immune Responses、COVID-19 Clinical Research Studies

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.