A safe and broad-spectrum SARS-CoV-2 mRNA vaccine with a new delivery system for in-situ expression

📖 Top 20% JournalSep 6, 2025Virologica Sinica

A safe and widely effective COVID-19 mRNA vaccine using a new delivery method for local protein production

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Abstract

The cumulative number of confirmed COVID-19 cases has surpassed 778 million, with over 7 million deaths.

A new lipid nanoparticle (LNP) system, WNP, enhances safety by reducing pro-inflammatory factors in the liver.
WNP facilitates in situ expression at the injection site, which may improve vaccine effectiveness.
An antigen designed with five key mutations can stimulate a broad range of antibodies against SARS-CoV-2.
WNP elicits a humoral immunity response comparable to that of SM-102, alongside a stronger cellular immune response.
This platform may aid in developing vaccines for other pathogens and responding to emerging mammalian viruses.

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Since the outbreak of COVID-19 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 indicate 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.

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Abstract

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