Development of an LNP-Encapsulated mRNA-RBD Vaccine against SARS-CoV-2 and Its Variants.

Development of an LNP-Encapsulated mRNA-RBD Vaccine against SARS-CoV-2 and Its Variants.
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DOI:
10.3390/pharmaceutics14051101
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发表时间:
2022-05-20
期刊:
影响因子:
5.4
通讯作者:
Wang, Peng George
Wang, Peng George
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Cong;Rcheulishvili, Nino;Shen, Zhigao;Papukashvili, Dimitri;Xie, Fengfei;Wang, Ziqian;Wang, Xingyun;He, Yunjiao;Wang, Peng George

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由严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)引起的2019冠状病毒病(COVID-19)无疑是本世纪最具挑战性的大流行病,仍然是全球卫生紧急事件。随着全球COVID-19病例数量不断上升,变种不断出现,疫苗需求迫切。在所有免疫方法中,mRNA疫苗在应对这一挑战方面表现出更有希望的结果。在此,我们设计了一种基于mRNA的疫苗,其编码SARS-CoV-2的受体结合结构域(RBD),并封装在脂质纳米颗粒(LNP)中。肌内(i.m.)mRNA-RBD疫苗的接种不仅引发了针对野生型SARS-CoV-2病毒的广谱中和抗体和细胞应答,还引发了针对Delta和Omicron变异体的广谱中和抗体和细胞应答。这些结果表明,两种剂量的mRNA-RBD免疫在小鼠中赋予了针对野生型SARS-CoV-2的强免疫应答,而加强剂量提供了针对SARS-CoV-2及其变体的足够免疫。综上所述,本研究中提出的mRNA-RBD疫苗的三剂量方案策略似乎是开发靶向SARS-CoV-2变体的mRNA疫苗的有希望的参考。
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is undoubtedly the most challenging pandemic in the current century and remains a global health emergency. As the number of COVID-19 cases in the world is on the rise and variants continue to emerge, there is an urgent need for vaccines. Among all immunization approaches, mRNA vaccines have demonstrated more promising results in response to this challenge. Herein, we designed an mRNA-based vaccine encoding the receptor-binding domain (RBD) of SARS-CoV-2 encapsulated in lipid nanoparticles (LNPs). Intramuscular (i.m.) administration of the mRNA-RBD vaccine elicited broad-spectrum neutralizing antibodies and cellular responses against not only the wild-type SARS-CoV-2 virus but also Delta and Omicron variants. These results indicated that two doses of mRNA-RBD immunization conferred a strong immune response in mice against the wild-type SARS-CoV-2, while the booster dose provided a sufficient immunity against SARS-CoV-2 and its variants. Taken together, the three-dose regimen strategy of the mRNA-RBD vaccine proposed in the present study appears to be a promising reference for the development of mRNA vaccines targeting SARS-CoV-2 variants.
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