Novel pseudorabies virus variant with defects in TK, gE and gI protects growing pigs against lethal challenge

One of the distinct features of the emerging Chinese pseudorabies virus (PRV) variant is its ability to cause severe neurological signs and high mortality in growing pigs in Bartha-K61-vaccinated pig farms. Either single- or multiple-gene-deleted live vaccine candidates have been developed; however, none was evaluated thoroughly in growing pigs. Here, we generated rSMX Delta gI/gE Delta TK, an attenuated PRV variant with defects in TK, gI and gE genes. The growth kinetics of the attenuated virus was similar to the wild type (wt) strain. It was safe for 1-day-old piglets. Twenty one-day-old weaned pigs were immunized intramuscularly either with 10(6.0) TCID50 of rSMX Delta gI/gE Delta TK or one dose of commercial Bartha-K61 vaccine, or with DMEM, and were challenged intranasally with 10(7.0) TCID50 wt virus at 28 days post vaccination. rSMX Delta gI/gE Delta TK elicited higher level neutralization antibody against both PRV variant SMX and Bartha-K61 strain, while Bartha-K61 vaccine elicited lower neutralization activity of antibody against SMX. After challenge, all pigs in rSMX Delta gI/gE Delta TK group survived without any clinical signs, while unvaccinated group showed 100% mortality, and Bartha-K61 group showed severe respiratory symptoms and 3 out of 5 pigs exhibited severe neurological signs. Pigs in rSMX Delta gI/gE Delta TK group gained significantly higher body weight and diminished viral excretion titer and period, compared with Bartha-K61 group. Furthermore, the safety and efficacy of rSMX Delta gI/gE Delta TK was also evaluated in sheep and compared with local vaccine in growing pigs. These data suggest that the attenuated strain rSMX Delta gI/gE Delta TK is a promising live marker vaccine candidate for PR control in the context of emerging PRV variants. (C) 2015 Elsevier Ltd. All rights reserved.