Design of SARS-CoV-2 hFc-Conjugated Receptor-Binding Domain mRNA Vaccine Delivered via Lipid Nanoparticles
Design of SARS-CoV-2 hFc-Conjugated Receptor-Binding Domain mRNA Vaccine Delivered via Lipid Nanoparticles
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DOI：
10.1021/acsnano.0c10180
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发表时间：
2021-01-22
期刊：
影响因子：
17.1
通讯作者：
Peer, Dan
中科院分区：
文献类型：
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作者：
Elia, Uri;Ramishetti, Srinivas;Peer, Dan
严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）已被确定为COVID-19的病原体，并处于当前全球人类大流行的中心，死亡人数超过100万。对疫苗的迫切需求导致了各种免疫方法的发展。mRNA疫苗代表了一种无细胞、简单和快速的免疫平台，因此已在最近的研究中用于SARS-CoV-2疫苗的开发。在此，我们提出了一种mRNA疫苗的设计，基于脂质纳米颗粒（LNPs）封装的SARS-CoV-2人Fc缀合受体结合结构域（RBD-hFc）。已经在荧光素酶（luc）mRNA报告基因测定中在体内评价了几种可电离脂质，并且已经选择了两种领先的LNP制剂用于随后的RBD-hFc mRNA疫苗策略。肌内注射LNP RBD-hFc mRNA在BALB/c小鼠中引起强烈的体液应答、高水平的中和抗体和Th 1偏向的细胞应答。目前研究中的数据表明，这些脂质通常是基于LNP的mRNA疫苗，特别是COVID 19疫苗的有希望候选物。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the causal agent of COVID-19 and stands at the center of the current global human pandemic, with death toll exceeding one million. The urgent need for a vaccine has led to the development of various immunization approaches. mRNA vaccines represent a cell-free, simple, and rapid platform for immunization, and therefore have been employed in recent studies toward the development of a SARS-CoV-2 vaccine. Herein, we present the design of an mRNA vaccine, based on lipid nanoparticles (LNPs)-encapsulated SARS-CoV-2 human Fc-conjugated receptor-binding domain (RBD-hFc). Several ionizable lipids have been evaluated in vivo in a luciferase (luc) mRNA reporter assay, and two leading LNPs formulations have been chosen for the subsequent RBD-hFc mRNA vaccine strategy. Intramuscular administration of LNP RBD-hFc mRNA elicited robust humoral response, a high level of neutralizing antibodies and a Th1-biased cellular response in BALB/c mice. The data in the current study demonstrate the potential of these lipids as promising candidates for LNP-based mRNA vaccines in general and for a COVID19 vaccine in particular.