title: Novel pseudorabies virus variant with defects in TK, gE and gI protects growing pigs against lethal challenge.
abstract: 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 rSMXΔgI/gEΔTK, 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 rSMXΔgI/gEΔTK 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. rSMXΔgI/gEΔTK 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 rSMXΔgI/gEΔTK 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 rSMXΔgI/gEΔTK group gained significantly higher body weight and diminished viral excretion titer and period, compared with Bartha-K61 group. Furthermore, the safety and efficacy of rSMXΔgI/gEΔTK was also evaluated in sheep and compared with local vaccine in growing pigs. These data suggest that the attenuated strain rSMXΔgI/gEΔTK is a promising live marker vaccine candidate for PR control in the context of emerging PRV variants.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Rui-Ming
authors.initials: RM
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Song
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Er-Chao
authors.initials: EC
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Mei-Mei
authors.initials: MM
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Qi-Gai
authors.initials: QG
authors.lastname: He
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Huan-Chun
authors.initials: HC
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address: wub@mail.hzau.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address: lzf6789@mail.hzau.edu.cn.
authors.forename: Zheng-Fei
authors.initials: ZF
authors.lastname: Liu
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001835:Body Weight; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D017353:Gene Deletion; D011558:Herpesvirus 1, Suid / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D007273:Injections, Intramuscular; D011557:Pseudorabies / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012756:Sheep; D016019:Survival Analysis; D013552:Swine; D013553:Swine Diseases / Q000276:immunology / Q000517:prevention & control*; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D022581:Vaccines, Marker / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D022581:Vaccines, Marker; D014764:Viral Proteins; D014765:Viral Vaccines
keywords: Efficacy; Growing pigs; Marker vaccine; PRV variant; Safety