A lyophilized anti-rabies mRNA-LNP vaccine induces early and robust immune responses from a single-dose subcutaneous administration.

Abstract

Rabies is a zoonotic disease caused by the rabies virus (RABV). RABV infections cause severe destruction to the central nervous system with fatal consequences, which has prompted global efforts to develop a highly effective and safe vaccine. Currently, the most widely used vaccines are inactivated vaccines, which need multiple injected doses for either pre-exposure prophylaxis or post-exposure immunization. This adds a lot of unnecessary trouble and labor costs. mRNA vaccines represent a promising platform against emerging and re-emerging infectious diseases, because they can induce high levels of virus-neutralizing antibodies (VNAs). In this study, we obtained a highly effective expression of rabies glycoprotein mRNA molecule by the optimized mRNA preparation procedure and encapsulated with lipid nanoparticles (LNP), termed mRNA-LNP vaccine. A single dose of the mRNA-LNP was highly immunogenic and induced a rapid protective antibody response in mice. Antibodies play a pivotal role in protecting against lethal RABV infections and eliminate the virus by blocking it from invading the CNS. One dose of the mRNA-LNP vaccine induced higher and more durable VNA titers in dogs and cats compared with the licensed inactivated vaccines, intriguingly, the antibody titers were higher in cats than in dogs. Furthermore, the immunogenicity of the freeze-dried vaccine was not significantly declined when compared with a freshly prepared vaccine, and it can be stored at -20℃ for 4 months. All the above results show that the mRNA-LNP vaccine is safe and effectively exhibited robust immune responses both for dogs and cats with a single-dose administration, which being promising to be a candidate vaccine against rabies.