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

## TL;DR

This study shows that an mRNA vaccine targeting the rabies virus G-protein using lipid nanoparticles is more effective than current vaccines in mice.

## Contribution

The novel contribution is the development of a muscle-targeting LNP-based mRNA vaccine for rabies with superior immunogenicity in mice.

## Key findings

- RV-G mRNA was significantly expressed in vitro.
- High virus-IgG and neutralizing antibody titers were induced in mice.
- The mRNA vaccine outperformed commercial vaccines in mice.

## Abstract

Background: 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 low single-dose neutralization titer, complex processes, and high costs. During the COVID-19 pandemic, the successful development of mRNA vaccines opened up a new avenue for preventive vaccines. As a new technology, mRNA has higher scalability. Methods: In this study, we designed an mRNA encoding the RV-G protein, encapsulated by our own muscle-targeting lipid nanoparticles (LNPs), and evaluated the expression of the RV-G protein in vitro, its immunogenicity, and its protection against virus infection in vivo. Results: The results show 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 showed that the RV-G mRNA vaccine is better than commercially available vaccines in mice. Conclusions: Our research highlights the potential of the mRNA-LNP platform in developing next-generation rabies vaccines.