An mRNA-LNP Vaccine Encoding the E^rns-E1-E2 Polyprotein Confers Complete Protection Against Bovine Viral Diarrhea...

Bovine viral diarrhea virus (BVDV) remains a major barrier to sustainable livestock development. Conventional BVDV vaccines are limited by inherent drawbacks such as potential virulence reversion and insufficient protective efficacy, which severely hamper global BVDV eradication efforts. mRNA vaccine technology, characterized by high expression efficiency, a favorable safety profile, and scalable manufacturing, offers a promising platform for next-generation BVDV vaccine development. In this study, we developed an mRNA-LNP vaccine candidate (E^rns/E1/E2 vaccine) encoding the full-length structural glycoproteins E^rns, E1 and E2, and systematically evaluated its immunogenicity and protective efficacy in BALB/c mice. The E2 extracellular domain-human IgG1 Fc fusion mRNA vaccine (E2/IgG1 vaccine) and a commercial inactivated BVDV vaccine served as controls. Our results demonstrated that the E^rns/E1/E2 vaccine elicited significantly higher neutralizing antibody titers (log₁₀NT₅₀ = 2.50 ± 0.082) and lymphocyte proliferation responses (stimulation index = 6.927 ± 0.145) than both control vaccines at 28 days post-primary vaccination (two weeks post-booster). Notably, no viral RNA was detected in any tissue or blood samples from E^rns/E1/E2-immunized mice at any time point following BVDV challenge, indicating complete immune protection against viral infection, whereas viral loads were consistently detected in multiple tissues of both control groups. These findings establish the E^rns/E1/E2 vaccine as a highly promising BVDV vaccine candidate and provide critical experimental support for advancing mRNA-based BVDV vaccine development.