title: Construction and evaluation of live attenuated myxoma virus vaccines with targeted virulence gene deletions.
abstract: Three deletion mutant viruses were constructed as potential vaccines against myxomatosis using the naturally attenuated Uriarra strain of myxoma virus. The viruses had the M007 (encodes a secreted gamma-interferon receptor homologue), M010 (encodes an epidermal growth factor homologue) and M011 (encodes an inhibitor of apoptosis in T lymphocytes) genes insertionally inactivated as either DeltaM007, DeltaM010/M011 or DeltaM007/M010/M011. All three viruses induced high serum antibody titres. Rabbits immunized with these deletion mutants were protected from lethal challenge. However, immunization of adult rabbits with DeltaM007 or DeltaM010/M011 was associated with mild clinical signs that would make these viruses unacceptable as vaccines. The triple gene knock-out virus (DeltaM007/M010/M011) termed Ur-TKO was very well tolerated by adult and juvenile rabbits. The low pathogenicity of Ur-TKO was confirmed by pathogenesis studies in domestic and wild rabbits.
authors.affiliation: School of Biochemistry and Molecular Biology, College of Science, The Australian National University, Canberra, ACT 0200, Australia.
authors.forename: Mathew M
authors.initials: MM
authors.lastname: Adams
authors.forename: Barbara H
authors.initials: BH
authors.lastname: van Leeuwen
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kerr
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000502:physiology; D002460:Cell Line; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000235:genetics / Q000276:immunology; D017353:Gene Deletion; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000276:immunology; D009154:Mutation / Q000235:genetics / Q000276:immunology; D009233:Myxoma virus / Q000235:genetics* / Q000276:immunology*; D009500:Neutralization Tests; D011213:Poxviridae Infections / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control; D011817:Rabbits; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014709:Vero Cells; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000235:genetics* / Q000276:immunology*; D037521:Virulence Factors / Q000235:genetics* / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D017471:Receptors, Interferon; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D037521:Virulence Factors; D004815:Epidermal Growth Factor