NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Stemirna Therapeutics, Shanghai, China.
Signal Transduct Target Ther. 2021 May 31;6(1):213. doi: 10.1038/s41392-021-00634-z.
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.
尽管全球已推出 COVID-19 疫苗接种计划，但仍迫切需要安全有效的疫苗，以确保所有国家都能公平、平等地获得供应。在这里，我们报告了一种高效的 mRNA 疫苗 SW0123 的开发情况，该疫苗由编码全长 SARS-CoV-2 刺突蛋白的序列修饰 mRNA 组成，封装在核壳结构的脂多聚物纳米颗粒（LPP）中。SW0123 易于使用大规模基于微流控的设备进行生产。独特的核壳结构纳米颗粒有助于疫苗摄取，并表现出高胶体稳定性和理想的生物分布模式，肌肉内给药时肝脏靶向作用低。在小鼠和非人灵长类动物中的广泛评估表明，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，还能够中和包括 D614G 和 N501Y 变体在内的一系列变体。此外，SW0123 在 SARS-CoV-2 攻毒后能够在小鼠和非人类灵长类动物中提供有效保护。总之，SW0123 是一种很有前途的疫苗候选物，有望在人类中进一步评估。
