Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine

Wu, Yangtao; Huang, Xiaofen; Yuan, Lunzhi; Wang, Shaojuan; Zhang, Yali; Xiong, Hualong; Chen, Rirong; Ma, Jian; Qi, Ruoyao; Nie, Meifeng; Xu, Jingjing; Zhang, Zhigang; Chen, Liqiang; Wei, Min; Zhou, Ming; Cai, Minping; Shi, Yang; Zhang, Liang; Yu, Huan; Hong, Junping; Wang, Zikang; Hong, Yunda; Yue, Mingxi; Li, Zonglin; Chen, Dabing; Zheng, Qingbing; Li, Shaowei; Chen, Yixin; Cheng, Tong; Zhang, Jun; Zhang, Tianying; Zhu, Huachen; Zhao, Qinjian; Yuan, Quan; Guan, Yi; Xia, Ningshao

A safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.