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

Ren YangYao DengBaoying HuangLei HuangAng LinYuhua LiWenling WangJingjing LiuShuaiyao LuZhenzhen ZhanYufei WangRuhan AWen WangPeihua NiuLi ZhaoShiqiang LiXiaopin MaLuyao ZhangYujian ZhangWeiguo YaoXingjie LiangJin-Cun ZhaoZhongmin LiuXiao-Zhong PengHangwen LiWenjie Tan
Published in: Signal transduction and targeted therapy (2021)
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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