A glycoprotein D-targeted lipid nanoparticle-encapsulated mRNA vaccine elicits strong protective immunity against pseudorabies virus

The emergence of virulent pseudorabies virus (PRV) variants and the insufficient cross-species protection conferred by conventional live attenuated vaccines pose significant challenges to global swine production and zoonotic biosecurity. Here, we developed a lipid nanoparticle-encapsulated mRNA vaccine (gD mRNA-LNPs) targeting PRV glycoprotein D (gD), a critical mediator of viral entry. This vaccine elicits robust neutralizing antibodies and potent T-cell responses, providing complete protection against lethal PRV challenge in both murine and porcine models. Unlike traditional vaccines, gD mRNA-LNPs eliminates residual pathogenicity risks and demonstrates broad efficacy against diverse PRV strains, including emerging variants. Its scalable production platform and ability to differentiate vaccinated from infected animals via serological diagnostics align with One Health strategies for PRV eradication. This study establishes mRNA-LNPs technology as a versatile, safe, and effective solution for combating PRV, with implications for improving livestock health and reducing zoonotic spillover threats.