A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity

Yang, Ren; Deng, Yao; Huang, Baoying; Huang, Lei; Lin, Ang; Li, Yuhua; Wang, Wenling; Liu, Jingjing; Lu, Shuaiyao; Zhan, Zhenzhen; Wang, Yufei; A, Ruhan; Wang, Wen; Niu, Peihua; Zhao, Li; Li, Shiqiang; Ma, Xiaopin; Zhang, Luyao; Zhang, Yujian; Yao, Weiguo; Liang, Xingjie; Zhao, Jincun; Liu, Zhongmin; Peng, Xiaozhong; Li, Hangwen; Tan, Wenjie

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.