Development of a potent mRNA vaccine against porcine epidemic diarrhea virus infection.

Porcine epidemic diarrhea virus (PEDV) is a highly contagious alphacoronavirus that poses a severe threat to neonatal piglets, often resulting in mortality rates of 80-100%. Despite the availability of inactivated and live attenuated vaccines, these formulations have demonstrated limited efficacy, allowing persistent PEDV circulation and recurrent outbreaks that cause substantial economic losses in the global swine industry. Here, we describe the development of an mRNA vaccine encapsulated in lipid nanoparticles (mRNA-LNP) that expresses a modified PEDV spike protein (S-6P). This vaccine elicits robust immune responses in mice, as well as in adult and neonatal pigs. Furthermore, the S-6P mRNA vaccine surpasses commercial vaccines in inducing PEDV-specific IgG, IgA, and neutralizing antibodies, and outperforms the standard sequential immunization regimen combining inactivated and live attenuated vaccines. It confers strong protection against a highly virulent PEDV GIIa strain (PEDV-WH2) in directly vaccinated piglets, as well as in neonates passively immunized via maternal antibodies from vaccinated sows. Collectively, these findings highlight the potential of mRNA-based vaccines as an innovative and effective platform for controlling lethal viral diseases in animal agriculture.