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

Signal Transduct Target Ther. 2021 May 31;6(1):213. doi: 10.1038/s41392-021-00634-z.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • COVID-19 / immunology*
  • COVID-19 / prevention & control
  • COVID-19 / virology
  • COVID-19 Vaccines / immunology*
  • COVID-19 Vaccines / therapeutic use
  • Female
  • Humans
  • Immunogenicity, Vaccine / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / pathogenicity
  • 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
  • mRNA Vaccines

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Synthetic
  • Viral Vaccines
  • spike protein, SARS-CoV-2