Abstract / Summary
Hepatitis E virus (HEV) genotypes 3 and 4 are major zoonotic pathogens, with domestic pigs serving as an important reservoir. Vaccination of pigs may therefore help reduce HEV circulation and zoonotic transmission. We evaluated the protective efficacy of an Escherichia coli-produced HEV-3 virus-like particle (VLP), HEV-3_p495, against homologous HEV-3 and heterologous HEV-4 challenge in pigs. Juvenile pigs vaccinated three times with either 80 or 400 μg of HEV-3_p495 remained negative for HEV RNA in serum and feces during prolonged cohabitation with naturally HEV-3-infected pigs, whereas all non-vaccinated controls became infected. At market age, vaccination also provided strong protection against intravenous HEV-3 challenge, with complete protection against detectable infection in the four-dose group and in two of three pigs in the three-dose group. Importantly, HEV-3_p495 conferred cross-protection against HEV-4 following cohabitation exposure. Two-dose vaccination prevented detectable infection in two of three young pigs and delayed fecal virus detection without viremia in the remaining pig. At market age, all vaccinated pigs remained negative for HEV RNA in serum and feces following HEV-4 exposure, whereas all non-vaccinated controls became infected. These findings provide proof-of-concept evidence for homologous and cross-genotype protection by HEV-3_p495 and support its further evaluation as a candidate swine vaccine for reducing HEV infection and shedding.