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

• Published in: Signal transduction and targeted therapy Vol. 6; no. 1; pp. 213 - 10
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.05.2021; Nature Publishing Group
• Subjects: 631/250/590; 692/308/575; Animals; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Biodistribution; Cancer Research; Cell Biology; Coronaviruses; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 - virology; COVID-19 vaccines; COVID-19 Vaccines - immunology; COVID-19 Vaccines - therapeutic use; Female; Humans; Immunogenicity, Vaccine - immunology; Internal Medicine; Lymphocyte Activation - immunology; Medicine; Medicine & Public Health; Mice; mRNA Vaccines; Oncology; Pathology; SARS-CoV-2 - immunology; SARS-CoV-2 - pathogenicity; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - antagonists & inhibitors; Spike Glycoprotein, Coronavirus - immunology; Th1 Cells - immunology; Th1 Cells - virology; Vaccines, Synthetic - immunology; Vaccines, Synthetic - therapeutic use; Viral Vaccines - immunology
• ISSN: 2059-3635; 2095-9907; 2059-3635
• 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.