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

An, Yaling; Li, Shihua; Jin, Xiyue; Han, Jian-bao; Xu, Kun; Xu, Senyu; Han, Yuxuan; Liu, Chuanyu; Zheng, Tianyi; Liu, Mei; Yang, Mi; Song, Tian-zhang; Huang, Baoying; Zhao, Li; Wang, Wen; Ruhan, A; Cheng, Yingjie; Wu, Changwei; Huang, Enqi; Yang, Shilong; Wong, Gary; Bi, Yuhai; Ke, Changwen; Tan, Wenjie; Yan, Jinghua; Zheng, Yong-tang; Dai, Lianpan; Gao, George F.

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 μg or 50 μg 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.