Pathogenicity and immunogenicity of a gE/gI/TK gene-deleted pseudorabies virus variant in susceptible animals

• We generated a gE/gI/TK-deleted mutant rPRVTJ-delgE/gI/TK based on a PRV variant.
• rPRVTJ-delgE/gI/TK displayed higher safety than rPRVTJ-delgE/gI in susceptible animals.
• rPRVTJ-delgE/gI/TK induced antibodies and protection comparable to rPRVTJ-delgE/gI.

A pseudorabies virus (PRV) variant with enhanced pathogenicity has emerged in many vaccinated swine herds in China since 2011. rPRVTJ-delgE/gI, a previously described gE/gI-deleted PRV based on the PRV variant TJ strain, has been shown to be avirulent to pigs yet virulent to sheep. To ensure desirable biosafety, we further deleted the thymidine kinase (TK) gene of rPRVTJ-delgE/gI to generate a gE/gI/TK-deleted mutant rPRVTJ-delgE/gI/TK, and evaluated its pathogenicity and immunogenicity in susceptible animals. Groups of mice (n = 5), sheep (n = 3), and pigs (n = 4) were inoculated with different doses of rPRVTJ-delgE/gI/TK or rPRVTJ-delgE/gI, and clinical signs, viral shedding, pathological changes, and serum antibodies were examined following inoculation. The results showed that rPRVTJ-delgE/gI/TK displayed higher safety than rPRVTJ-delgE/gI for mice (103–106 TCID50) and sheep (105 TCID50), and pigs inoculated with rPRVTJ-delgE/gI/TK (105 TCID50) induced PRV-specific antibodies and protection against lethal PRV challenge comparable to those immunized with rPRVTJ-delgE/gI. In conclusion, rPRVTJ-delgE/gI/TK has the potential to be developed as a vaccine for controlling the currently prevalent PR in China.