Nanoparticle Vaccines Based on the Receptor Binding Domain (RBD) and Heptad Repeat (HR) of SARS-CoV-2 Elicit Robust Protective Immune Responses.

Nanoparticle Vaccines Based on the Receptor Binding Domain (RBD) and Heptad Repeat (HR) of SARS-CoV-2 Elicit Robust Protective Immune Responses.
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基于 SARS-CoV-2 受体结合域 (RBD) 和七肽重复序列 (HR) 的纳米颗粒疫苗可引发强大的保护性免疫反应。

DOI:
10.1016/j.immuni.2020.11.015
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发表时间:
2020-12-15
期刊:
影响因子:
32.4
通讯作者:
Zhang H
Zhang H
中科院分区:
医学1区
文献类型:
--
作者:
Ma X;Zou F;Yu F;Li R;Yuan Y;Zhang Y;Zhang X;Deng J;Chen T;Song Z;Qiao Y;Zhan Y;Liu J;Zhang J;Zhang X;Peng Z;Li Y;Lin Y;Liang L;Wang G;Chen Y;Chen Q;Pan T;He X;Zhang H

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为应对全球COVID-19大流行,已提出各种疫苗策略,每种策略均具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铁蛋白共价结合到严重急性呼吸综合征冠状病毒-2(SARS-CoV-2)刺突(S)蛋白的受体结合结构域(RBD)和/或七肽重复(HR)亚基来开发纳米颗粒疫苗。与单体疫苗相比,纳米颗粒疫苗引起更强的中和抗体和细胞免疫应答。用RBD和/或RBD-HR纳米颗粒接种的hACE 2转基因小鼠在SARS-CoV-2攻击后表现出肺中病毒载量降低。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应答。在加强免疫之前,恒河猴的纳米颗粒疫苗接种诱导了中和抗体以及T和B细胞应答;这些应答持续超过三个月。因此,基于RBD和HR的纳米颗粒提出了一种有前途的针对SARS-CoV-2和其他冠状病毒的疫苗接种方法。RBD和HR纳米颗粒疫苗诱导有效的中和抗体应答纳米颗粒疫苗保护小鼠免受SARS-CoV-2感染HR抗原引发体液和细胞免疫应答纳米颗粒内的HR抗原有助于交叉保护性免疫Ma et al.利用SpyTag/SpyCatcher系统构建两种基于铁蛋白的纳米颗粒疫苗,其将RBD和HR抗原结合在SARS-CoV-2刺突蛋白中。RBD和RBD-HR纳米颗粒疫苗比单体疫苗引起更有效的中和抗体应答和更强的T细胞免疫应答。含有HR的纳米颗粒诱导针对其他冠状病毒的交叉反应性免疫应答。
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. RBD and HR nanoparticle vaccines induce potent neutralizing antibody responses Nanoparticle vaccines protect against SARS-CoV-2 infection in mice HR antigens elicit both humoral and cellular immune responses HR antigens within nanoparticles contribute to cross-protective immunity Ma et al. construct two Ferritin-based nanoparticle vaccines that conjugate RBD and HR antigens in SARS-CoV-2 Spike protein utilizing the SpyTag/SpyCatcher system. RBD and RBD-HR nanoparticles vaccines elicit more potent neutralizing antibody responses and stronger T cell immune responses than monomers. HR-containing nanoparticles induce cross-reactive immune responses against other coronaviruses.
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