the potential risk linked to the use of modified live viruses for antirabies
vaccination of foxes
In northern countries, sylvatic rabies is a zoonotic disease (a disease
whose epidemiology is solely linked to a wildlife reservoir). In Western
Europe, the main vector is the red fox (Vulpes vulpes). Here, vector
refers to the animal host that is most susceptible to rabies in a region
at a given time and that is solely responsible for maintaining the infection.
The control of the infection within the vector species thus permits overall
control of the infection and, most importantly, reduces the risk of transmission
to man. In Western Europe, control measures to reduce fox populations
were only temporarily effective and did not prevent the disease from spreading.
For this reason, other methods such as oral immunisation of foxes needed
to be assessed. Research has focused on oral vaccination, the only means
allowing the immunisation of a sufficient proportion (75%) of wild foxes,
through the distribution of vaccine baits.
Since 1978, several European countries have conducted, at different times,
large-scale field trials of oral vaccination of foxes (Vulpes vulpes)
against rabies, using the SAD, standard or B19-modified attenuated strains
of rabies virus. The use of attenuated strains of rabies virus remains
controversial as far as safety and stability are concerned, since these
virus strains retain pathogenicity for rodents or other wildlife species
and are heat-sensitive. To improve both safety and stability of the vaccine
used in the field, a recombinant vaccinia virus expressing the immunogenic
G protein of rabies virus has been developed and released in the field.
The vaccinia-rabies recombinant virus was called VVTGgRAB. We have studied
the safety and efficacy of this recombinant virus in field trials and
in vaccination efforts.
Red fox (Vulpes vulpes).
Approach and methodology
Taking into account all the available experimental data concerning the
safety of the VVTGgRAB for target and non target species and its efficacy
in foxes, initial limited field trials of fox vaccination were authorised
first by the Belgian and then by the French public health authorities.
In the Belgian trial (17-18 October, 1987) a total of 250 vaccine baits
(chicken heads) were delivered manually on a 6 km2 area situated
in the central part of a military zone. With the safety of the VVTGgRAB
being confirmed by this small trial, the Belgian authorities agreed to
an enlarged open field trial. This was conducted in a 435 km2
area in the southern part of the country, chosen because it has the lowest
average human population density in the country (42 inhabitants km-2)
as well as high rabies incidence in foxes. Furthermore, the region is
characterised by various habitats housing most of the animal species liable
to consume bait. Each bait contained a suspension of 108 CCID50
of VVTGgRAB (2.2 ml by volume) within a plastic sachet and 150 mg tetracycline
as a long-term biomarker of bait uptake. After the vaccination campaign,
222 dead wild animals belonging to 19 species were collected in the vaccination
area. After necropsy, the following tissues were removed: brain for rabies
diagnosis, jaws for tetracycline detection and blood for the titration
of vaccinia and rabies antibodies.
Main findings and outcome
Following this enlarged trial, three fox-vaccination campaigns using VVTGgRAB
were then carried out in Belgium in November 1989, April 1990 and October
1990 in order to check for efficacy in an area of 2200 km2
with a mean baiting density of 15 baits km-2. These campaigns
have brought a drastic decrease in the incidence of rabies both in foxes
and in domestic animals. The only perceived remaining risk was a recombinant
event between the recombinant virus and a wild orthopoxvirus such as cowpox.
A serological survey was done on sera collected from foxes and experimental
infections of foxes with cowpox were performed in order to assess this
perceived risk showing that is was negligible.
All the safety studies during deliberate release trials, done step by
step, using the vaccinia-rabies recombinant virus for oral vaccination
of foxes against rabies led to the same conclusion: the recombinant vaccinia-rabies
virus is perfectly safe and safer than any other attenuated rabies virus
strain presently used in the field in Western Europe. The use of the recombinant
vaccinia-rabies virus did lead to the elimination of rabies in large areas
and, as a consequence a drastic decrease in human post-exposure treatments.
Serological surveys and experimental studies in foxes have shown that
the risk of recombination between the recombinant vaccinia-rabies virus
and wild orthopoxvirus could be considered as nearly nil.
Brochier B., Kieny M.P., Costy F., Coppens P., Bauduin B., Lecocq
J.P., Languet B, Chappuis G., Desmettre P., Afiademanyo K., Libois
R., Pastoret P.P., Large-scale eradication of rabies using
recombinant vaccinia-rabies vaccine.
1991, pp. 520-522.
Pastoret P.P., Brochier B., Languet B., Thomas I., Paquot A., Bauduin
B., Costy F., Antoine H., Kieny M.P., Lecocq J.P., Debruyn J., Desmettre
Ph., First field trial of fox vaccination against rabies with
a vaccinia-rabies recombinant virus.
Vet. Rec., 123,
1988, pp. 481-483.
Brochier B., Thomas I., Bauduin B., Leveau T., Pastoret P.P., Languet
B., Chappuis G., Desmettre P., Blancou J., Artois M., Use
of vaccinia-rabies recombinant virus for the oral vaccination of
foxes against rabies.
1990, pp. 101-104.
Boulanger D., Brochier B., Crouch A., Bennett M., Gaskell R.M.,
Baxby D., Pastoret P.P., Comparison of the susceptibility
of the red fox (Vulpes vulpes) to a vaccinia-rabies recombinant
virus and to cowpox virus.
1995, pp. 215-219.
Boulanger D., Crouch A., Brochier B., Bennett M., Clément
J., Gaskell R.M., Baxby D., Pastoret P.P., Serological survey
for Orthopoxvirus infection of wild mammals in areas where a recombinant
vaccinia-rabies virus is used to vaccinate foxes against rabies.
Vet. Rec., 138, 1996, p. 2.
January 1989 December 1990
University of Liège (BE)
Centre National dEtudes sur la Rage et la Pathologie des Animaux