A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity.
A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity.
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DOI：
10.1038/s41392-021-00634-z
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发表时间：
2021-05-31
影响因子：
39.3
通讯作者：
Tan W
中科院分区：
文献类型：
--
作者：
Yang R;Deng Y;Huang B;Huang L;Lin A;Li Y;Wang W;Liu J;Lu S;Zhan Z;Wang Y;A R;Wang W;Niu P;Zhao L;Li S;Ma X;Zhang L;Zhang Y;Yao W;Liang X;Zhao J;Liu Z;Peng X;Li H;Tan W
尽管全球已开始接种新冠肺炎疫苗，但仍迫切需要安全有效的疫苗，以确保各国公平公平地供应疫苗。在这里，我们报道了一种高效的mRNA疫苗SW0123的开发，它由编码全长SARS-CoV-2刺突蛋白的序列修饰的mRNA组成，包装在核壳结构的脂多糖(LPP)纳米颗粒中。SW0123很容易使用基于大规模微流体的设备来生产。独特的核壳结构纳米粒有利于疫苗的接种，具有高的胶体稳定性和理想的生物分布模式，肌肉注射时具有较低的肝脏靶向性。在小鼠和非人类灵长类动物中的广泛评估显示，SW0123具有很强的免疫原性，表现为诱导Th1极化的T细胞反应和高水平的抗体，这些抗体不仅能够中和野生型SARS-CoV-2，而且能够中和包括D614G和N501Y变异体在内的一系列变异体。此外，SW0123在小鼠和非人灵长类动物中对SARS-CoV-2的攻击都具有有效的保护作用。综上所述，SW0123是一种有希望的候选疫苗，有可能在人类身上进行进一步的评估。
Although inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core–shell structured lipopolyplex (LPP) nanoparticles. SW0123 is easy to produce using a large-scale microfluidics-based apparatus. The unique core–shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability, and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration. Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123, represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2, but also a panel of variants including D614G and N501Y variants. In addition, SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge. Taken together, SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.
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