4.7 Article

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

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SPRINGERNATURE
DOI: 10.1038/s41392-021-00634-z

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资金

  1. National Key Research and Development Program of China [2016YFD0500301, 2020YFC0840900, 2020YFC0842200]
  2. National Natural Science Foundation of China [82041041, 82061138008]
  3. Shanghai Pujiang Talent Program [2020PJD068]
  4. Stemirna Therapeutics

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SW0123 is a highly efficacious mRNA vaccine candidate with strong immunogenicity, inducing T cell and antibody responses, capable of neutralizing multiple variants, and providing effective protection in animal challenge experiments.
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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