The Deletion of US3 Gene of Pseudorabies Virus (PRV) Delta gE/TK Strain Induces Increased Immunogenicity in Mice

Re-emerging pseudorabies (PR) caused by pseudorabies virus (PRV) variant has been prevailing among immunized herds in China since 2011, indicating that commercially available PR vaccine strains couldn't provide complete protection against novel, epidemic PRV variant. Before this study, a gE/TK-gene-deleted virus (PRV Delta gE/TK) was constructed from PRV QYY2012 variant through homologous recombination and Cre/LoxP system. Here, PRV Delta gE/TK/US3 strain was generated by deleting US3 gene based on PRV Delta gE/TK strain using the same method. The growth characteristics of PRV Delta gE/TK/US3 were analogous to that of PRV Delta gE/TK. Moreover, the deletion of US3 gene could promote apoptosis, upregulate the level of swine leukocyte antigen class I molecule (SLA-I) in vitro, and relieve inflammatory response in inoculated BALB/c mice. Subsequently, the safety and immunogenicity of PRV Delta gE/TK/US3 was evaluated as a vaccine candidate in mice. The results revealed that PRV Delta gE/TK/US3 was safe for mice, and mice vaccinated with PRV Delta gE/TK/US3 could induce a higher level of PRV-specific neutralizing antibodies and cytokines, including IFN-gamma, IL-2 and IL-4, also higher level of CD8(+) CD69(+) Tissue-Resident Memory T cells (TRM). The results show that the deletion of US3 gene of PRV Delta gE/TK strain could induce increased immunogenicity, indicating that the PRV Delta gE/TK/US3 strain is a promising vaccine candidate for preventing and controlling of the epidemic PR in China.