An mRNA-LNP Vaccine Encoding the Erns-E1-E2 Polyprotein Confers Complete Protection Against Bovine Viral Diarrhea Virus in Mice

Abstract

Simple Summary Bovine viral diarrhea virus (BVDV) is a major obstacle to sustainable cattle farming worldwide, but current vaccines are limited by the risk of regaining virulence and by insufficient protective efficacy, which together hamper global efforts to eradicate the disease. To solve this problem, we developed a messenger RNA vaccine delivered in lipid nanoparticles that encodes the three full-length structural glycoproteins (Erns, E1 and E2) of BVDV and evaluated its immune response and protective efficacy in mice, comparing it against both a second messenger RNA candidate and a commercial inactivated vaccine. The new vaccine elicited significantly higher neutralizing antibody titers and stronger lymphocyte proliferation responses than either control. Most importantly, when vaccinated mice were later exposed to the live virus, no trace of the virus was found in any of their tissues or blood, demonstrating the new vaccine provided complete protection, while the comparison groups still carried the virus in multiple tissues. These findings show that this messenger RNA vaccine is a highly promising candidate for protecting cattle against this devastating disease, potentially offering a safer, more effective tool to protect cattle and support the global effort to control and eliminate BVDV.