Construction and evaluation of live attenuated myxoma virus vaccines with targeted virulence gene deletions.
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.
Adams
Mathew M
MM
School of Biochemistry and Molecular Biology, College of Science, The Australian National University, Canberra, ACT 0200, Australia.
van Leeuwen
Barbara H
BH
Kerr
Peter J
PJ
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
D051034:Inhibitor of Apoptosis Proteins; D017471:Receptors, Interferon; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D037521:Virulence Factors; D004815:Epidermal Growth Factor