A Minimally Replicative Vaccine Protects Vaccinated Piglets Against Challenge With the Porcine Epidemic Diarrhea Virus

摘要

Porcine epidemic diarrhea virus (PEDV), is an economically important enteric coronavirus, with over a 90% mortality rate in neonatal piglets. The virus emerged in the U.S in 2013, resulting in severe production losses. Effective vaccine development against PEDV is a challenge. Inactivated vaccines are of questionable efficacy. Attenuated vaccines, while more effective, require a relatively long lead development time, are associated with safety concerns and are also unable to prevent new field outbreaks. To combine the safety and efficacy advantages of inactivated and attenuated PEDV vaccines respectively, in this study, we tested the hypothesis that subjecting PEDV virions to heat treatment at 44oC for 10 mins to reversibly unfold structural proteins, followed by exposure to RNAse to fragment the genome, would result in a vaccine preparation with intact viral structure/ antigenicity but highly diminished replicative abilities. We expected the vaccine to be both safe and effective in a piglet challenge model. Following the heat and RNAse treatment, PEDV virions had an intact electron microscopic ultrastructure and were amplified only in the 3rd passage in Vero cells, indicating that diminished replication was achieved in vitro. Strong PEDV spike-protein specific and virus neutralizing antibody responses were elicited in vaccinated piglets. Upon challenge, all vaccinated pigs were protected against fecal viral shedding and intestinal pathology, while the unvaccinated controls were not. The vaccine virus was not detected in the fecal matter of vaccinated pigs prior to challenge; nor did they develop intestinal lesions. Thus, the described approach has significant promise in improving current approaches for PEDV immunization.