A Novel Trivalent BVDV mRNA Vaccine Displayed by Virus-like Particles Eliciting Potent and Broad-Spectrum Antibody Responses.

Background/Objectives: Bovine viral diarrhea virus (BVDV) causes significant economic losses in the cattle industry worldwide. The current vaccines have limited efficacy against diverse BVDV genotypes. Currently, multi-antigen target design and nanocarrier display technologies can provide ideas for broad-spectrum and efficient BVDV vaccine design. Methods: Here we developed a trivalent mRNA vaccine encoding the domains I-II of envelope glycoprotein E2 from three BVDV genotypes (3E2), introduced with bovine IgG1 Fc (bFc), STABILON (hStab), and artificial virus-like particle (ARVLP) containing CD80 transmembrane (TM) domain, FcγRII cytoplasmic domain, and WW domain of ITCH. Then, in vitro expression, in vivo immunogenicity and neutralizing antibody analysis were performed to evaluate the vaccines. Results: The in vitro expression results showed that bFc and hStab dramatically enhanced antigen expression and immunogenicity. In addition, the ARVLP further enhanced the secretion and potency of neutralizing antibodies. Finally, the immunogenicity of the bFc_BVDV_3E2_ARVLP_hStab mRNA vaccine was evaluated in mice, guinea pigs, and lactating goats and high levels of neutralizing antibodies against all three BVDV genotypes were detected. Conclusions: Our trivalent design strategy with bFc, hStab, and ARVLP shows highly efficient expression as well as strong immunogenicity and provides a promising approach for next-generation BVDV vaccines with broader and stronger protection.