A Safe and Broad-spectrum SARS-CoV-2 mRNA Vaccine with a New Delivery System for In-situ Expression.

Since the outbreak of SARS-CoV-2 in late 2019, the cumulative number of confirmed cases worldwide has surpassed 778 million, and the number of deaths has exceeded 7 million, posing a significant threat to human life and health while inflicting enormous losses on the global economy. At the stage where sequential immunization is recommended, there is a pressing demand for mRNA vaccines that can be rapidly adapted to new sequences, are easy to industrialize, and exhibit high safety and effectiveness. We developed a lipid nanoparticle (LNP) system, designated as WNP, which facilitates essentially in situ expression at the injection site and results in lower levels of pro-inflammatory factors in the liver, thus enhancing its safety compared to liver-targeted alternatives. Furthermore, in light of the swiftly mutating characteristic of SARS-CoV-2, a study has used cross-lineage chimeras and mutation patch strategies to design an antigen that is highly immunogenic and can stimulate the production of a broad range of effective antibodies. Therefore, we used the same antigenic configuration of RBD including five key mutation sites (K417T, L452R, T478K, E484K, and N501Y) to achieve optimal broad-spectrum efficacy. Our results indicated that WNP can elicit a humoral immunity response that is as robust as that of SM-102, a stronger cellular immune response, and provide a certain protective effect. On top of that, WNP can be applied to the development of vaccines targeting other pathogens and will contribute to a quicker response to the spillovers of unknown mammalian viruses.