A rabies mRNA vaccine provides a rapid and long-term immune response in mice

Rabies is a fatal viral disease caused by the rabies virus (RABV), with a case fatality rate in humans of almost 100%. Vaccinations are the most effective method of preventing and controlling rabies. Currently, the most widely used vaccines are all inactivated vaccines, which require considerable time and money to produce. A messenger RNA (mRNA)-based vaccine is a rapid and versatile platform for relatively easy vaccine production on a large scale. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) vaccine encoding a rabies virus glycoprotein (RABV-G). Two doses of the mRNA-B-LNP vaccine were highly immunogenic and induced robust immune responses and robust Tfh and GC B cellular response as well as a Th1-biased cellular immune response in mice and protected mice against the rabies virus. A single dose of the mRNA-B-LNP vaccine induced a rapid and long-term protective antibody response in mice. Compared to the inactivated vaccine, a single dose of the mRNA-B-LNP vaccine induced higher neutralizing antibody titers in dogs, and two doses of the mRNA-B-LNP vaccine induced a durable humoral response in dogs. Additionally, the mRNA-B-LNP vaccine as a liquid formulation can be stored at 2 − 8 °C for 2 months.