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.

doi:10.1101/2020.12.18.423552

bioRxiv · 10.1101/2020.12.18.423552

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.

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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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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.. 2020-12-20. Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine. https://doi.org/10.1101/2020.12.18.423552

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