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During recent years, most research on the control of sylvatic rabies has concentrated on developing methods of oral vaccination of wild rabies vectors. To improve both the safety and the stability of the vaccine used, a recombinant vaccinia virus, which expresses the immunising glycoprotein of rabies virus (VRG), has been developed and tested extensively in the laboratory as well as in the field. From 1989 to 1995, approximately 8.5 million VRG vaccine doses were dispersed in Western Europe to vaccinate red foxes (Vulpes vulpes), and in the United States of America (USA) to vaccinate raccoons (Procyon lotor) and coyotes (Canis latrans). In Europe, the use of VRG has led to the elimination of sylvatic rabies from large areas of land, which have consequently been freed from the need for vaccination. Nevertheless, despite very good examples of cross-border cooperation, reinfections have occurred in some regions, due to the difficulty of co-ordinating vaccination plans among neighbouring countries. In the USA, preliminary data from field trails indicate a significant reduction in the incidence of rabies in vaccinated areas.

Wildlife vaccination depends on vaccines which can be orally administered by a baiting system. Therefore only two possibilities exist: either the use of attenuated strains of viruses, or recombinant vector viruses. As far as rabies is concerned, the choice of the recombinant vaccinia-rabies virus was made because it was safer and more stable. An in vitro stability study of the recombinant product compared to wild rabies virus at different temperatures (4 degrees C, 20 degrees C, 37 degrees C, 45 degrees C) showed that the recombinant virus was more stable. The stability of the recombinant virus was also tested under field conditions; besides natural freezing and thawing cycles, the virus titre remained unchanged in the bait for a month. Taking into account the fact that all baits are eaten by wild animals within this period, one can assume that the vaccine is efficacious for all baiting animals in field conditions. The stability of the recombinant vaccinia-rabies vaccine is of considerable interest in such uncontrolled conditions.

This paper presents data derived from safety and efficacy studies of ALVAC-based rabies and feline leukemia virus (FeLV) vaccine candidates in target species. Inoculation of the ALVAC-RG recombinant was well tolerated in all species including humans and very young dogs. Protection induced in dogs against rabies challenge was long-lasting and could be elicited in the face of high levels of maternally-derived neutralizing antibody. Parenteral inoculation of cats with an ALVAC-FeLV recombinant was safe and induced protection against persistent infection following oro-nasal FeLV challenge.

The efficacy of a vaccinia-rabies recombinant virus (10(8) TCID50) contained in a machine-made baiting system has been tested in 22 captive young foxes which were divided into three experimental groups of six and a control group of four foxes. Each fox in groups 1, 2 and 3 were fed one, two and three vaccine-baits, respectively, on successive days. The four unvaccinated foxes were housed separately. As shown by the incorporation of a tetracycline biomarker into their bones, all the baited foxes ingested at least one bait. Thirty days after baiting seroconversion to rabies was observed in 15 (83 per cent) of the foxes and seroconversion to vaccinia in 14 (78 per cent). Sixteen of the 18 (89 per cent) baited foxes resisted a rabies challenge 30 days after baiting. One cub was protected against rabies despite the absence of detectable anti-rabies antibody. The results demonstrate that the bait-sachet system permits a good release of the virus suspension into the mouth.

One of the most promising ways to control rabies in wildlife seems to be the distribution of bait containing an anti-rabies vaccine. So far, the most widely used vaccines were modified live viruses (SAD strain or derivatives). Nevertheless, these strains retain some pathogenicity for non-target species. A novel vaccine was proposed consisting of genetically modified vaccinia virus (strain Copenhagen, thermosensitive ts 26) expressing the foreign glycoprotein G for the rabies virus (strain ERA). Different doses of this recombinant virus were administered orally to 59 foxes (Vulpes vulpes) and their antibodies were titrated before challenge. Foxes (8/8) resisted 1 month after vaccination with 10(7) plaque forming units (PFU), or 4/4 after 18 months. Seroconversion among dogs was 4/4 after vaccination with 10(9,6) PFU and 4/4 among cats after vaccination with 10(8) PFU. These dogs (4/4) and cats (3/4) resisted the challenge 2-3 months after vaccination. This vaccine thus appears to be potent and safe in these species. Its properties are discussed.

Campaigns of fox vaccination against rabies were carried out in Belgium, grand-duchy of Luxembourg and France in September 1986, June and September 1987. The SAD B19 attenuated strain of rabies virus, contained in baits (Tübingen baits) was used as vaccine. Baits were distributed at a range density of 11 to 15 baits per km2. First results are very encouraging. A recombinant vaccinia virus harbouring the rabies virus glycoprotein gene has been developed. This recombinant virus can be given to the fox by the oral route and protects it against rabies virus challenge; it is also innocuous for the fox and other non-target European species. A first trial of fox vaccination against rabies using this recombinant vaccinia-rabies virus has been carried out in Belgium, on a military domain, in October 1987.

The pathogenicity of a vaccinia recombinant virus expressing the rabies glycoprotein (VVTGgRAB) was tested in several wild animal species which could compete with the natural rabies host, the red fox (Vulpes vulpes) in consuming vaccine baits in Europe. The following species were included in this study: wild boar (Sus scrofa), Eurasian badger (Meles meles), wood mouse (Apodemus sylvaticus), yellow-necked mouse (Apodemus flavicollis), bank vole (Clethrionomys glareolus), common vole (Microtus arvalis), field vole (Microtus agrestis), water vole (Arvicola terrestris), common buzzard (Buteo buteo), kestrel (Falco tinnunculus), carrion crow (Corvus corone), magpie (Pica pica) and jay (Garrulus glandarius). During the observation period, the 107 animals given the VVTGgRAB vaccine orally did not show any clinical signs. Daily monitoring for 28 days and postmortem examination did not result in the detection of pox lesions in the oral mucosa or the skin in mammals or the unfeathered portions of birds. VVTGgRAB seems to multiply in the mammalian species tested, since rabies seroconversion was observed in all of them. Birds failed to develop demonstrable rabies virus-neutralizing antibody. A seroconversion against vaccinia virus was observed in two of four wild boars. Serological results obtained in badgers and wild boars also demonstrates the absence of direct or indirect horizontal transmission of the recombinant virus. The potential of the recombinant virus for the immunization of badgers against rabies also was investigated. Only 50% of the badgers orally administered with 1 x 10(8.3) TCID50 of this vaccine were protected against rabies.