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.

DR5 is a restriction factor for human herpesviruses.

Restriction factors are dominant proteins that target different essential steps of the viral life cycle; thus, these proteins provide an early line of defense against viruses. Here, we found that the internalization of DR5, an important receptor of the extrinsic apoptotic pathway, initiates apoptosis to inhibit Kaposi sarcoma-associated herpesvirus (KSHV) lytic replication. An evolutionary analysis of the DR5 sequence demonstrated that three amino acids underwent positive selection in primates.