A single-dose mRNA vaccine provides a long-term protection for hACE2 transgenic mice from SARS-CoV-2.

A single-dose mRNA vaccine provides a long-term protection for hACE2 transgenic mice from SARS-CoV-2.
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单剂量 mRNA 疫苗为 hACE2 转基因小鼠提供长期保护,使其免受 SARS-CoV-2 的侵害

DOI:
10.1038/s41467-021-21037-2
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发表时间:
2021-02-03
影响因子:
16.6
通讯作者:
Yan J
Yan J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Huang Q;Ji K;Tian S;Wang F;Huang B;Tong Z;Tan S;Hao J;Wang Q;Tan W;Gao GF;Yan J

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COVID-19大流行的迅速蔓延使SARS-CoV-2疫苗的开发成为全球卫生和经济的优先事项。利用多功能性和快速发展的优势,三种SARS-CoV-2 mRNA候选疫苗已进入临床试验,采用两剂免疫方案。然而,SARS-CoV-2感染后恢复期患者的抗体应答减弱以及人类再次感染的出现引起了人们对SARS-CoV-2疫苗保护期可能较短的广泛关注。在这里,我们开发了一种脂质包裹形式的核苷修饰的mRNA疫苗,编码SARS-CoV-2 RBD,称为mRNA-RBD。mRNA-RBD的单次免疫引起了强烈的中和抗体和细胞应答,并在hACE 2转基因小鼠的肺中赋予了对野生型SARS-CoV-2感染的几乎完全的保护。值得注意的是,在血清转移研究中,mRNA-RBD疫苗接种诱导的BALB/c小鼠中高水平的中和抗体可维持至少6.5个月,并赋予hACE 2转基因小鼠对SARS-CoV-2感染的长期显著保护作用。这些数据表明,单剂mRNA-RBD可提供针对SARS-CoV-2攻击的长期保护。针对SARS-CoV-2的几种基于mRNA的疫苗正处于临床开发的后期阶段。在这里,作者表明,用表达SARS-CoV-2刺突RBD的mRNA疫苗进行单次免疫接种,诱导中和抗体,这些抗体至少维持6.5个月,并在小鼠血清转移研究中提供保护。
The rapid expansion of the COVID-19 pandemic has made the development of a SARS-CoV-2 vaccine a global health and economic priority. Taking advantage of versatility and rapid development, three SARS-CoV-2 mRNA vaccine candidates have entered clinical trials with a two-dose immunization regimen. However, the waning antibody response in convalescent patients after SARS-CoV-2 infection and the emergence of human re-infection have raised widespread concerns about a possible short duration of SARS-CoV-2 vaccine protection. Here, we developed a nucleoside-modified mRNA vaccine in lipid-encapsulated form that encoded the SARS-CoV-2 RBD, termed as mRNA-RBD. A single immunization of mRNA-RBD elicited both robust neutralizing antibody and cellular responses, and conferred a near-complete protection against wild SARS-CoV-2 infection in the lungs of hACE2 transgenic mice. Noticeably, the high levels of neutralizing antibodies in BALB/c mice induced by mRNA-RBD vaccination were maintained for at least 6.5 months and conferred a long-term notable protection for hACE2 transgenic mice against SARS-CoV-2 infection in a sera transfer study. These data demonstrated that a single dose of mRNA-RBD provided long-term protection against SARS-CoV-2 challenge. Several mRNA-based vaccines for SARS-CoV-2 are in late phase clinical development. Here, the authors show that a single immunization with a mRNA vaccine expressing SARS-CoV-2 spike RBD induces neutralizing antibodies that are maintained for at least 6.5 months and confer protection in a sera transfer study in mice.
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发表时间: 2018-04
期刊: Nature reviews. Drug discovery
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