title: Generation of an attenuated Tiantan vaccinia virus by deletion of the ribonucleotide reductase large subunit.
abstract: Attenuation of the virulence of vaccinia Tiantan virus (VTT) underlies the strategy adopted for mass vaccination campaigns. This strategy provides advantages of safety and efficacy over traditional vaccines and is aimed at minimization of adverse health effects. In this study, a mutant form of the virus, MVTT was derived from VTT by deletion of the ribonucleotide reductase large subunit (R1) (TI4L). Compared to wild-type parental (VTT) and revertant (VTT-rev) viruses, virulence of the mutant MVTT was reduced by 100-fold based on body weight reduction and by 3,200-fold based on determination of the intracranial 50% lethal infectious dose. However, the immunogenicity of MVTT was equivalent to that of the parental VTT. We also demonstrated that the TI4L gene is not required for efficient replication. These data support the conclusion that MVTT can be used as a replicating virus vector or as a platform for the development of vaccines against infectious diseases and for cancer therapy.
authors.affiliation: Institute of Military Veterinary Medicine, Academy of Military Medical Sciences of PLA, Jilin, People's Republic of China, Kansf10@mails.jlu.edu.cn.
authors.forename: Shifu
authors.initials: S
authors.lastname: Kan
authors.forename: Peng
authors.initials: P
authors.lastname: Jia
authors.forename: Lili
authors.initials: L
authors.lastname: Sun
authors.forename: Ningning
authors.initials: N
authors.lastname: Hu
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.forename: Huijun
authors.initials: H
authors.lastname: Lu
authors.forename: Mingyao
authors.initials: M
authors.lastname: Tian
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Qi
authors.forename: Ningyi
authors.initials: N
authors.lastname: Jin
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D001835:Body Weight; D005260:Female; D007928:Lethal Dose 50; D008807:Mice, Inbred BALB C; D021122:Protein Subunits / Q000235:genetics; D012264:Ribonucleotide Reductases / Q000235:genetics*; D017384:Sequence Deletion; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D021122:Protein Subunits; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated; D012264:Ribonucleotide Reductases