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

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.

Animals↗

Biological control of the rabbit in Australia: lessons not learned?

The story of the spread of the European rabbit across Australia, and of the two viruses used to control it, is an interesting way to look at some of the issues associated with biological control. What can be learned from the way this system developed, and what has been learned, or not learned, from the mistakes made? Here, we look at these events and examine what insights can be gained from this history.

Animals↗

A reappraisal of the role of mosquitoes in the transmission of myxomatosis in Britain.

Field experiments were made in southern England to re-examine the possibility that mosquitoes in Britain might feed on wild rabbits and hence be vectors of myxomatosis. Mosquitoes of several species were attracted to rabbits enclosed in cylindrical traps and in a trap in which the animal was placed in a wire mesh cage. Substantial numbers of mosquitoes were also caught biting, or attempting to bite, tethered rabbits which were not in cages or traps. Evidence that mosquitoes fed on wild rabbits under natural conditions was obtained from results of precipitin tests made on blood-smears collected from mosquitoes caught resting amongst vegetation. On a few evenings mosquitoes were seen to be attracted to healthy wild rabbits and apparently attempting to feed on them. Batches of two mosquito species collected from the field were infected with myxoma virus.It was concluded that contrary to previous beliefs mosquitoes in Britain feed to a certain extent on wild rabbits, and therefore are potential vectors of myxomatosis. No attempts were made to assess their relative importance in the transmission of the disease, which in Britain is transmitted mainly by the rabbit flea.

Animals↗

Myxomatosis: the introduction of the European rabbit flea Spilopsyllus cuniculi (Dale) into wild rabbit populations in Australia.

1. The European rabbit flea Spilopsyllus cuniculi (Dale) bred successfully in wild rabbits on three properties in New South Wales and, within two breeding seasons, almost every rabbit shot within a quarter of a mile of a release site was infested.2. It was demonstrated that the flea transmitted myxoma virus in the field.3. In areas where more than 75% of the rabbits shot at the beginning of the breeding season were flea-infested and myxoma virus was present, populations failed to show the expected summer build-up.

Agriculture↗

Myxomatosis: some observations on breeding the European rabbit flea Spilopsyllus cuniculi (Dale) in an animal house.

Rabbit fleas for use in Myxomatosis investigations have been successfully bred on rabbits in an animal house. The timing of emergence appeared to be governed by a biological timing control interacting with different forms of disturbance. Yield was found to be related to litter size, the time the doe and her kittens were removed from the nest, the number of fleas put onto a doe before littering and the mean ambient temperature to which the doe was exposed in the week pre-partum. The survival rate of fleas in storage was affected by temperature, the degree of crowding, moisture content of the containers, whether fleas were fed or unfed and the source of fleas in terms of emergence times.

Animals↗

Myxomatosis in the Mallee region of Victoria, Australia.

Sharp reductions in the wild rabbit (Oryctolagus cuniculus (L.)) population in the Mallee are associated with annual myxomatosis epizootics. The extent to which the population reductions are the direct result of the epizootics varies with time of epizootic occurrence. All grazing animals in the Mallee are under nutritional stress each summer and autumn. When the epizootic occurs during the early summer heavy losses occur in a previously healthy population. Similar losses which occur in the late summer and autumn are the result of a nutritional stress - epizootic complex. The end result in each case is a population reduction of about 80%. This reduction occurs in a population which is the most resistant to myxomatosis known in Victoria and in association with epizootics caused by field strains of myxoma virus of moderate virulence only. The earlier summer epizootics are of considerable economic importance because they sharply reduce the pressure on the limited food available for other grazing animals.

Animals↗

Myxomatosis: the occurrence of antibody to a soluble antigen of myxoma virus in wild rabbits, Oryctolagus cuniculus (L.), in Victoria, Australia.

The occurrence of antibody of myxoma virus in wild rabbits following epizootics is highest in the semi-arid north-west of Victoria and lowest in temperate southern Victoria. Occurrence ranges up to about 90% in the north-west and to about 70% in the south except on the Western Plains where epizootics are rare and antibody occurrence seldom exceeds 30%. The establishment of the European rabbit flea may be changing the pattern of occurrence of antibody in the north-west by causing spring outbreaks of myxomatosis. It is suggested that the effects of the replacement of a simple recurring system of epizootic and breeding season several months apart by the occurrence of myxomatosis twice in the same year, once coincident with the breeding season, will be complex. The occurrence of detectable antibody may be less dependent on the infection rate and may be dependent to some extent on the relative timing of spring myxomatosis and the breeding season.

Animals↗

Myxomatosis: changes in the epidemiology of myxomatosis coincident with the establishment of the European rabbit flea Spilopsyllus cuniculi (Dale) in the Mallee region of Victoria.

Outbreaks of myxomatosis during the winter or spring have coincided with the establishment of the European rabbit flea in the Mallee region. The severity of these outbreaks has varied from causing complete suppression of the normal spring increase in rabbit numbers to being completely ineffective in a year in which late spring rains allowed rabbit breeding to extend into the early summer.In 1973 and 1974 effective spring myxomatosis caused heavy mortality in kittens before they emerged from the warrens. The age of the population increased as the result of few young rabbits coming into the population and of the lessened stress on old rabbits in a low summer-autumn population. This effect was reversed in the late-breeding year, 1976, when flea numbers were apparently too low to maintain a spring outbreak and rabbit numbers increased rapidly.

Age Factors↗

Myxomatosis: the release and spread of the European rabbit flea Spilopsyllus cuniculi (Dale) in the Central District of Victoria.

The European rabbit flea was first released in Victoria in August 1969 at Werribee. Releases were made on five different land forms. At one site the first flea was recovered 2 weeks after release. Fleas were recovered between 4 and 6 weeks after release at the other sites. Differences in establishment and spread on the different land forms were due to physically restricted movement of some rabbit populations. By June 1971 80% of rabbits were infested but an occasional young uninfested rabbit was still found in August 1978. Infestation numbers were higher than in the Mallee region especially on pregnant does.

Age Factors↗

Myxomatosis. The effect of age upon survival of wild and domestic rabbits (Oryctolagus cuniculus) with a degree of genetic resistance and unselected domestic rabbits infected with myxoma virus.

The response of wild and domestic rabbits with a degree of genetic resistance to myxomatosis has been shown to be markedly affected by the age at which they were infected with a virulent strain of the virus. The response, in terms of mean survival time and percentage survival, fell with increasing age from 10 to 30 weeks with little change thereafter.

Age Factors↗

Fluctuations in the titre of antibody to a soluble antigen of myxoma virus in field populations of rabbits, Oryctolagus cuniculus (L.), in Australia.

Results are presented on tests carried out over the past 5 years to measure the antibody titre of various rabbit populations to a soluble antigen of myxoma virus. In an unexpectedly high percentage of immune rabbits the antibody fell below measurable titres, and later rose to measurable titres without the advent of an observable epizootic of myxomatosis. The re-stimulation of the immune response is discussed in terms of re-infection and virus reactivation.

Animals↗

Myxomatosis: passive immunity in the offspring of immune rabbits (Oryctolagus cuniculus) infested with fleas (Spilopsyllus cuniculi Dale) and exposed to myxoma virus.

Kittens with maternal antibodies to myxoma virus, the offspring of rabbits which had recovered from myxomatosis, were exposed to fleas contaminated with myxoma virus and/or contact with infected rabbits from birth. All kittens died or became infected before 8 weeks of age. When compared with adult animals similarly infected the kittens showed no advantage in terms of survival time or recovery rate attributable to maternal antibodies. Flea transmission of virus was found more effective than contact transmissions.

Animals↗

The differential transmissibility of Myxoma virus strains of differing virulence grades by the rabbit flea Spilopsyllus cuniculi (Dale).

Laboratory studies showed that few rabbit fleas (Spilopsyllus cuniculi (Dale)) transmitted myxomatosis after removal from wild rabbits (Oryctolagus cuniculus (L) that had been infected for fever than 10-12 days, irrespective of the virulence of the myxoma virus strain involved. Rabbits infected with fully virulent (Grade I) strains died within 10-15 days and few fleas from these hosts became infective; averaging all the samples takem. 12% of the fleas were infective. Also, few fleas acquired infectivity on individual rabbits which covered from infection with attenuated strains; the mean was 8% infective. Rabbits which died between 17 and 44 days after infection had higher proportions of infective fleas at all sampling times; the mean was 42% infective. Male and female fleas transmitted virus with equal efficiency. For rabbits infected with any of the attenuated virus strains the mean percentage of infective fleas was inversely related to the survival time of the host. Rabbits infected with moderately attenuated strains (Grades IIIA and IIIB) had, on average, the highest proportion of infective fleas; hence such strains have a selective advantage and have become predominant under natural conditions in Britain. The changes that might occur if there is an increase in host resistance to myxomatosis are discussed.

Animals↗

Myxomatosis on the Western Plains of Victoria.

Myxomatosis on the Western Plains is an enzootic disease in contrast with the epizootic pattern which is general in eastern Australia. The most unusual aspects are the presence of significant numbers of diseased rabbits throughout the winter and the continuously low percentage of rabbits with antibodies to myxoma virus. Climatic and topographic conditions are unsuited to the production of the high densities of mosquitoes necessary for widespread epizootics. Under these conditions the effects of less efficient methods of myxomatosis transmission are apparent. The unusual epidemiology of myxomatosis has resulted in selection for virulence of the virus similar to that which has occurred under summer epizootic conditions. All field strains are now in the mid range of virulence.

Animals↗