Safety evaluation of a recombinant myxoma-RHDV virus inducing horizontal transmissible protection against myxomatosis and rabbit haemorrhagic disease

Abstract

We have recently developed a transmissible vaccine to immunize rabbits against myxomatosis and rabbit haemorrhagic disease based on a recombinant myxoma virus (MV) expressing the rabbit haemorrhagic disease virus (RHDV) capsid protein [Bárcena et al. Horizontal transmissible protection against myxomatosis and rabbit haemorragic disease using a recombinant myxoma virus. J. Virol. 2000;74:1114-23]. Administration of the recombinant virus protects rabbits against lethal RHDV and MV challenges. Furthermore, the recombinant virus is capable of horizontal spreading promoting protection of contact animals, thus providing the opportunity to immunize wild rabbit populations. However, potential risks must be extensively evaluated before considering its field use. In this study several safety issues concerning the proposed vaccine have been evaluated under laboratory conditions. Results indicated that vaccine administration is safe even at a 100-fold overdose. No undesirable effects were detected upon administration to immunosuppressed or pregnant rabbits. The recombinant virus maintained its attenuated phenotype after 10 passages in vivo.

Genome Comparison of a Nonpathogenic Myxoma Virus Field Strain with Its Ancestor, the Virulent Lausanne Strain

“…Furthermore, no nucleotide changes had accumulated during the selection of the recombinant virus. This result was in agreement with our previous observations, indicating that both viruses exhibited indistinguishable biological features (6,7,56,57).…”

“…The results (data not shown) demonstrated that the 48 nucleotide changes monitored persisted after passages in either cell cultures or rabbits. This finding was in agreement with previous analysis on the biological and genetic stabilities of 6918VP60-T2 (6,56), further indicating that the attenuated nature of 6918VP60-T2 seems to be a stable trait. The molecular characterization of 6918 and 6918VP60-T2 is an important step toward the use of the recombinant virus as a vaccine against myxomatosis and RHD for wild-rabbit populations.…”

“…Interestingly, M135R is one of the seven MV genes absent in SFV (13,61). It is noteworthy that the clinical symptoms induced by vMyx135KO (10) closely resemble those previously described for 6918 or the derived recombinant virus 6918VP60-T2 (6,7,56,57), strongly suggesting that disruption of M135R is an important determinant of 6918 attenuation.…”

“…It has been used for the development of a "transmissible vaccine" intended to protect wild-rabbit populations against both myxomatosis and rabbit hemorrhagic disease virus (RHDV) in Spain, where the European rabbit plays a key role in the Mediterranean ecosystems (18). For this purpose, a recombinant virus, 6918VP60-T2, was constructed by inserting the capsid gene of RHDV into the genome of strain 6918 (4,6,7,56,57). The genomes of 6918 and 6918VP60-T2 have been sequenced.…”

Construction and testing of a novel host-range defective myxoma virus vaccine with the M063 gene inactivated that is non-permissive for replication in rabbit cells

“…Further trials would be needed to optimize the vaccine dose and boosting regime. In addition, Ur M063 could be further genetically engineered to express the Rabbit Haemorrhagic Disease Virus capsid gene under the control of an early promoter by replacing the gptgus fusion gene and thus potentially provide protection against the two major viral diseases of rabbits as has been previously described for a recombinant myxoma virus [2,4,29].…”