A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates.

A tandem-repeat dimeric RBD protein-based covid-19 vaccine zf2001 protects mice and nonhuman primates.
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DOI:
10.1080/22221751.2022.2056524
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发表时间:
2022-12
影响因子:
13.2
通讯作者:
--
中科院分区:
医学2区
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--
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在大规模的疫苗接种活动中,迫切需要安全、有效、可部署的疫苗来控制新冠肺炎。我们报道了一种已批准的新冠肺炎蛋白亚单位疫苗ZF2001的临床前研究,该疫苗含有串联重复二聚体受体结合结构域蛋白和明胶佐剂。我们评估了疫苗在小鼠和非人类灵长类动物(NHP)中的免疫原性和有效性。ZF2001诱导小鼠和非人灵长类动物产生高水平的RBD结合抗体和SARS-CoV-2中和抗体,并在NHP中诱导平衡的TH1/TH2细胞应答。通过减少病毒RNA和减轻肺损伤的检测,两种剂量的ZF2001可以保护Ad-hACE2转导的小鼠免受SARS-CoV-2感染。在NHP中,接种25 μg或50 μg ZF2001可防止肺部、气管和支气管感染SARS-CoV-2,肺部损害较轻。在两种动物模型中都没有观察到疾病增强的证据。ZF2001已被批准在乌兹别克斯坦、印度尼西亚和哥伦比亚的中国紧急使用。在这项临床前研究中发现的对小鼠和NHP的高安全性、免疫原性和保护效果与人类临床试验的结果一致。
Safe, efficacious, and deployable vaccines are urgently needed to control COVID-19 in the large-scale vaccination campaigns. We report here the preclinical studies of an approved protein subunit vaccine against COVID-19, 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 non-human primates, and 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 was observed in both animal models. ZF2001 has been approved for emergency use in China, Uzbekistan, Indonesia, and Columbia. The high safety, immunogenicity, and protection efficacy in both mice and NHPs found in this preclinical study was consistent with the results in human clinical trials.
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