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 γ-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 ΔM007, ΔM010/M011 or ΔM007/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 ΔM007 or ΔM010/M011 was associated with mild clinical signs that would make these viruses unacceptable as vaccines. The triple gene knock-out virus (ΔM007/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.