A tandem-repeat dimeric RBD protein-based COVID-19 vaccine ZF2001 protects mice and nonhuman primates

An, Y.; Li, S.; Jin, X.; Han, J.-B.; Xu, K.; Xu, S.; Han, Y.; Liu, C.; Zheng, T.; Liu, M.; Yang, M.; Song, T.-z.; Huang, B.; Zhao, L.; Wang, W.; A, R.; Cheng, Y.; Wu, C.; Huang, E.; Yang, S.; Wang, G.; Bi, Y.; Ke, C.; Tan, W.; Yan, J.; Zheng, Y.-T.; Dai, L.; Gao, G. F.

doi:10.1101/2021.03.11.434928

bioRxiv · 10.1101/2021.03.11.434928

A tandem-repeat dimeric RBD protein-based COVID-19 vaccine ZF2001 protects mice and nonhuman primates

An, Y.·Li, S.·Jin, X.·Han, J.-B.·Xu, K.·Xu, S.·Han, Y.·Liu, C.·Zheng, T.·Liu, M.·Yang, M.·Song, T.-z.·Huang, B.·Zhao, L.·Wang, W.·A, R.·Cheng, Y.·Wu, C.·Huang, E.·Yang, S.·Wang, G.·Bi, Y.·Ke, C.·Tan, W.·Yan, J.·Zheng, Y.-T.·Dai, L.·Gao, G. F.

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Abstract

A safe, efficacious and deployable vaccine is urgently needed to control COVID-19 pandemic. We report here the preclinical development of a COVID-19 vaccine candidate, ZF2001, which contains tandem-repeat dimeric receptor-binding domain (RBD) protein with alum-based adjuvant. We assessed vaccine immunogenicity and efficacy in both mice and non-human primates (NHPs). ZF2001 induced high levels of RBD-binding and SARS-CoV-2 neutralizing antibody in both mice and NHPs, and also elicited balanced TH1/TH2 cellular responses in NHPs. Two doses of ZF2001 protected Ad-hACE2-transduced mice against SARS-CoV-2 infection, as detected by reduced viral RNA and relieved lung injuries. In NHPs, vaccination of either 25 g or 50 g ZF2001 prevented infection with SARS-CoV-2 in lung, trachea and bronchi, with milder lung lesions. No evidence of disease enhancement is observed in both models. ZF2001 is being evaluated in the ongoing international multi-center Phase 3 trials (NCT04646590) and has been approved for emergency use in Uzbekistan.

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An, Y., Li, S., Jin, X., Han, J.-B., Xu, K., Xu, S., Han, Y., Liu, C., Zheng, T., Liu, M., Yang, M., Song, T.-z., Huang, B., Zhao, L., Wang, W., A, R., Cheng, Y., Wu, C., Huang, E., Yang, S., Wang, G., Bi, Y., Ke, C., Tan, W., Yan, J., Zheng, Y.-T., Dai, L., Gao, G. F.. 2021-03-11. A tandem-repeat dimeric RBD protein-based COVID-19 vaccine ZF2001 protects mice and nonhuman primates. https://doi.org/10.1101/2021.03.11.434928

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