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Nanoparticle Vaccines Based on the Receptor Binding Domain (RBD) and Heptad Repeat (HR) of SARS-CoV-2 Elicit Robust Protective Immune Responses
Immunity ( IF 32.4 ) Pub Date : 2020-11-25 , DOI: 10.1016/j.immuni.2020.11.015
Xiancai Ma , Fan Zou , Fei Yu , Rong Li , Yaochang Yuan , Yiwen Zhang , Xiantao Zhang , Jieyi Deng , Tao Chen , Zheng Song , Yidan Qiao , Yikang Zhan , Jun Liu , Junsong Zhang , Xu Zhang , Zhilin Peng , Yuzhuang Li , Yingtong Lin , Liting Liang , Guanwen Wang , Yingshi Chen , Qier Chen , Ting Pan , Xin He , Hui Zhang

Various vaccine strategies have been proposed in response to the global COVID-19 pandemic, each with unique strategies for eliciting immune responses. Here, we developed nanoparticle vaccines by covalently conjugating the self-assembled 24-mer ferritin to the receptor binding domain (RBD) and/or heptad repeat (HR) subunits of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spike (S) protein. Compared to monomer vaccines, nanoparticle vaccines elicited more robust neutralizing antibodies and cellular immune responses. RBD and RBD-HR nanoparticle vaccinated hACE2 transgenic mice vaccinated with RBD and/or RBD-HR nanoparticles exhibited reduced viral load in the lungs after SARS-CoV-2 challenge. RBD-HR nanoparticle vaccines also promoted neutralizing antibodies and cellular immune responses against other coronaviruses. The nanoparticle vaccination of rhesus macaques induced neutralizing antibodies, and T and B cell responses prior to boost immunization; these responses persisted for more than three months. RBD- and HR-based nanoparticles thus present a promising vaccination approach against SARS-CoV-2 and other coronaviruses.



中文翻译:

基于SARS-CoV-2受体结合域(RBD)和七肽重复(HR)的纳米疫苗可引发强大的保护性免疫反应。

已经针对全球COVID-19大流行提出了各种疫苗策略,每种策略都有引发免疫反应的独特策略。在这里,我们通过将自组装的24-mer铁蛋白与严重急性呼吸系统综合症冠状病毒2(SARS-CoV-2)的受体结合域(RBD)和/或七肽重复(HR)亚基共价缀合来开发纳米颗粒疫苗。刺突(S)蛋白。与单体疫苗相比,纳米颗粒疫苗引发了更强大的中和抗体和细胞免疫应答。接种了RBD和/或RBD-HR纳米颗粒的RBD和RBD-HR纳米颗粒接种的hACE2转基因小鼠在SARS-CoV-2攻击后肺中的病毒载量降低。RBD-HR纳米颗粒疫苗还促进了针对其他冠状病毒的中和抗体和细胞免疫反应。恒河猴的纳米级疫苗接种可诱导中和抗体,并在加强免疫之前对T和B细胞产生反应;这些反应持续了三个多月。因此,基于RBD和HR的纳米颗粒提供了一种针对SARS-CoV-2和其他冠状病毒的有前途的疫苗接种方法。

更新日期:2020-12-15
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