Comprehensive evaluation of the safety and immunogenicity of a gene-deleted variant pseudorabies virus attenuated vaccine

Pseudorabies virus (PRV) variant infections have caused a substantial economic impact on swine production in the absence of new powerful candidate vaccines. In this study, we developed and evaluated a gene-deleted variant pseudorabies virus (PRV)-attenuated vaccine, PRV GX-ΔTK/IES, in which the genes TK, gI, gE, US9 and US2 were deleted. During a study of innocuousness, all mice inoculated with PRV GX-ΔTK/IES survived, neither clinical signs nor pathological changes were observed, and viral genomes could not be detected in the blood and tissues. All piglets inoculated with high titres of PRV GX-ΔTK/IES remained clinically healthy, and neither fever nor clinical signs were observed. Viral detection results were negative in nasal swab samples, blood and tissue samples. Moreover, none of the cohabitated piglets seroconverted during a trial on horizontal transmission. The immunogenicity was assessed through a vaccination and challenge experiment in piglets. Piglets vaccinated with PRV GX-ΔTK/IES and the commercial vaccine were completely protected from subsequent PRV infection, and the level of immunity and protection induced by PRV GX-ΔTK/IES was better than that provided by the live commercial vaccine. Thus, PRV GX-ΔTK/IES is completely safe for both nontarget and target animals and can be regarded as a novel live gene-deleted PRV vaccine candidate.