Volume 6 Issue 6, Jun 2021:
Article
A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity
Ren Yang
ORCID: orcid.org/0000-0002-8134-4010,Yao Deng,Baoying Huang,Lei Huang,Ang Lin
ORCID: orcid.org/0000-0001-5662-1576,Yuhua Li,Wenling Wang,Jingjing Liu,Shuaiyao Lu,Zhenzhen Zhan,Yufei Wang,Ruhan A,Wen Wang,Peihua Niu,Li Zhao,Shiqiang Li,Xiaopin Ma,Luyao Zhang,Yujian Zhang,Weiguo Yao,Xingjie Liang,Jincun Zhao
ORCID: orcid.org/0000-0003-2515-5589,Zhongmin Liu,Xiaozhong Peng
ORCID: orcid.org/0000-0002-8564-0247,Hangwen Li &…Wenjie Tan
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.
