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HU, R.

Publications and source records attributed to HU, R..

2 recordsLinked to original sources

Immunogenicity of Rabies Virus G-Protein mRNA Formulated with Muscle Targeting Lipid Nanoparticles in Mice

Rabies is a preventable zoonotic disease caused by the rabies virus (RABV) with a high mortality rate. Most vaccines on the market or under development have issues such as a low single-dose neutralization titer, complex processes, and high costs. During the COVID-19 pandemic, the successful development of mRNA vaccines has opened up a new avenue for preventive vaccines. As a new technology, mRNA has higher scalability. In this study, we designed an mRNA encoding the RV-G protein, encapsulated by our own muscle targeting lipid nanoparticles (LNP), and evaluated the expression of the RV-G protein in vitro, its immunogenicity, and its protection against virus infection in vivo. The results showed that RV-G mRNA was significantly expressed in vitro. High Virus-IgG binding titers and Virus-neutralizing antibody titers (VNT) were induced by immunization with RV-G mRNA-LNP. Additionally, our results show that the RV-G mRNA vaccine is better than commercially available vaccines in mice.

pharmacology and toxicology↗

Efficacy and safety of an mRNA-based RSV preF vaccine in preclinical studies

The transmembrane fusion (F) protein of RSV plays important roles in RSV pathogenesis as it mediates the fusion between virus and the target cell membrane. During the fusion process, F protein transits from a metastable state (prefusion, preF) to a stable state after merging of virus and cell membranes (postfusion, postF). The majority of highly neutralizing antibodies induced by natural infection or immunization targets the preF form, making it the preferred antigen for vaccine development. Here, we evaluate the mRNA vaccine candidate, STR-V003, which encapsulates the modified mRNA encoding the preF protein in lipid nanoparticles (LNPs). This vaccine demonstrated robust immunogenic in both mice and cotton rats. STR-V003 induced high levels of neutralizing antibodies and RSV preF-specific IgG antibodies, and significantly reduced the RSV viral loads in the lung and nose tissue of challenged animals. In addition, STR-V003 did not have obvious enhancement of lung pathology without causing vaccine enhanced disease (VED). The repeated dose general toxicology studies and local tolerance studies of STR-V003 were evaluated in rats. Therefore, STR-V003 has an acceptable safety profile and robust protective immunity against RSV, and has been approved by the FDA to enter phase I clinical study (NCT06344975).

pharmacology and toxicology↗