Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine
wu, y.; Huang, X.; Yuan, L.; Wang, S.; Zhang, Y.; Xiong, H.; Chen, R.; Ma, J.; Qi, R.; Nie, M.; Xu, J.; Zhang, Z.; Chen, L.; Wei, M.; Zhou, M.; Cai, M.; Shi, Y.; Zhang, L.; Yu, H.; Hong, J.; Wang, Z.; Hong, Y.; Yue, M.; Li, Z.; Chen, D.; Zheng, Q.; Li, S.; Chen, Y.; Cheng, T.; Zhang, J.; Zhang, T.; Zhu, H.; Zhao, Q.; Yuan, Q.; Guan, Y.; Xia, N.
Show abstract
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.
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