Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007 1 Efficacy of a square...
14
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007 1 Efficacy of a square presentation of V-RG vaccine baits in red fox, domestic dog and raccoon dogs F. Cliquet 1 , A.L. Guiot 2 , C. Schumacher 3 , J. Maki 3 and J. Barrat 1 1 WHO Collaborating Centre for Research and Management in Zoonoses Control, OIE Reference Laboratory for Rabies, Community Reference Laboratory for Rabies Serology, AFSSA Malzéville, France 2 Conseils en Pharmacie et Biologie Santé, Lyon, France 3 Merial, Lyon (France) and Athens (USA)
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Transcript of Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007 1 Efficacy of a square...
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007
1
Efficacy of a square presentation of V-RG vaccine baits in red fox, domestic
dog and raccoon dogs
F. Cliquet1, A.L. Guiot2, C. Schumacher3, J. Maki3 and J. Barrat1
1 WHO Collaborating Centre for Research and Management in Zoonoses Control, OIE Reference Laboratory for Rabies, Community Reference Laboratory for Rabies Serology, AFSSA Malzéville, France2 Conseils en Pharmacie et Biologie Santé, Lyon, France3 Merial, Lyon (France) and Athens (USA)
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007
2
V-RG rabies vaccine
* V-RG vaccine (Raboral® V-RG) is a vaccinia virus recombinant coding for the rabies glycoprotein gene.
* V-RG vaccine baits have been extensively used in France and in other European countries which are all rabies free (France, 2000 ; Belgium and Luxembourg, 2001) and is currently used in US and also in Ukraine.
* This vaccine is one of the two vaccines recognised and recommended by the European Commission (2002) and WHO (2005) for oral vaccination of foxes against rabies.
Rectangular Fishmeal polymer
bait (France)for red foxes and
raccoon dogs (Merial)
Square Fishmeal or Chickenmeal
Polymer bait (USA)for raccoons,
coyotes and gray foxes (Merial)
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007
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To evaluate in captive animals (domestic dog, red fox and raccoon dog) the efficacy of a
square V-RG bait produced in USA in captive animals
Evaluation of : Attractiveness of the baits Induction of neutralising antibodies Protection after rabies challenge
Objective
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007
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Experimental design
Raccoon dogs
vaccinated controls
vaccinated controls
vaccinated controls
93
1010
109
square VRGplacebo bait
square VRGplacebo bait
square VRGNA
108.4 TCID50/dose-
108.4 TCID50/dose-
108.8 TCID50/dose-
D30New York rabies strain
D91Salivary gland homogenate
from rabid foxes, 400 MIC LD50
D214Salivary gland homogenate
from a naturally infected coyote (CDC), 1600 MIC LD50
Dogs
Foxes
NA : not administered
All animals daily observed and kept at least for 90 days after challenge
Number of animals
DO : Vaccination Vaccine titre Challenge
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007
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Results - Bait acceptability
Species
Dogs
Foxes
Raccoon dogs
Bait consumption invaccinates placebo
Bait uptaketime
8/91/9
10/10
10/10
1/32/3
10/10*
-
less than 1 hourless than 24 hours
less than 24 hours
mean time of disappearance4.2 hours
(SD = 7 hours)
* Doubtful for two foxes
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007
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Group Animal No. Day -12 Day 7 Day 14 Day 21 Day 28 Challenge
Day 120 Euthanasia Response to challenge
4 0,17 0,07 0,04 0,17 0,87 0,87 D (17)Controls 5 0,10 0,04 0,03 0,04 0,07 10,45 D (15)
6 < 0,03 0,04 0,03 0,04 0,07 D (14)GMT < 0,08 0,05 0,03 0,06 0,16 3,02SD 0,07 0,02 0,01 0,08 0,46 6,77
16 0,29 0,06 0,03 0,10 0,29 D (15)Vaccinated 17 < 0,07 0,06 0,29 1,99 3,46 0,87 S
18 < 0,06 0,03 0,06 0,10 0,22 0,50 S19 < 0,03 0,03 0,03 0,03 0,17 0,10 S20 < 0,04 0,03 0,03 0,10 0,13 0,38 S21 < 0,06 0,03 0,04 0,17 0,38 0,87 S22 > 0,87 0,04 0,04 0,06 0,10 0,22 S23 < 0,06 0,03 0,03 0,07 0,07 0,66 S24 0,13 0,04 0,04 0,13 0,22 0,87 S
GMT < 0,09 0,04 0,05 0,12 0,24 0,45SD 0,27 0,01 0,08 0,63 1,09 0,31
Rabies virus neutralising antibodies (IU/ml)
ResultsDogs : rabies virus neutralising antibodies and resistance to challenge
S : surviveD : die
• Only one dog out of 9 vaccinates seroconverted• All three controls died between D14 and D17• One vaccinate died at D15
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007
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ResultsFoxes : rabies virus neutralising antibodies
2 vaccinated foxes did not seroconvert
-2,0
-1,5
-1,0
-0,5
0,0
0,5
1,0
1,5
2,0
0 20 40 60 80 100 120 140 160 180 200
days after vaccination
me
an
of
FA
VN
ra
bie
s a
nti
bo
die
s (
log
I.U
./ml)
Square V-RG bait
Placebo square bait
Threshold of positivity
vaccination rabies challenge
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007
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ResultsFoxes : resistance to challenge
Vaccinated
Controls
Mean mortalitydelay (days)
14
14,40
Total
10
10
Rabies diagnosis(FAT + cell culture)
2 pos, 8 neg
10 pos
Dead
2
10
Group
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007
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ResultsRaccoon dogs : rabies virus neutralising antibodies
-1,5
-1,0
-0,5
0,0
0,5
1,0
1,5
2,0
0 50 100 150 200 250
days after vaccination
me
an
of
FA
VN
ra
bie
s a
nti
bo
die
s (
log
I.U
./ml)
Square V-RG bait
Control not vaccinated
Threshold of positivity
rabies challengevaccination
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007
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Vaccinated
Controls
Mean mortalitydelay (days)
-
18,90
Total
10
9
Rabies diagnosis(FAT + cell culture)
10 neg
9 pos
Dead
0
9
Group
ResultsRaccoon dogs : resistance to challenge
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007
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Discussion- The square fishmeal polymer bait V-RG is well accepted by dogs, foxes and raccoon dogs.
- The rate of seroconversion following bait uptake as well as the magnitude of antibody titres are different in the 3 species :
5.38(4.23)
Neutralising antibodies at D28
Dogs 0.07
0.03
1.51
3.46
41.59
13.77
0.24(1.09)
2.95(13.27)
1/9
7/9
10/10Raccoon dogs
Foxes
min (IU/ml)
max(IU/ml)
GMT(S.D.)
positive/total
The high levels of rabies antibodies observed in raccoon dogs have been also observed when vaccinated with an attenuated oral vaccine (Cliquet and al, 2006)
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007
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Discussion
- The challenge was validated since all controls died from rabies (typical rabies signs were observed and diagnostic tests positive).
- Protection after challenge was satisfactory in the three species tested.
* Dogs : protection (8/9 dog) despite absence of seroconversion already largely documented.
* Foxes : protection in 8/10 foxes ; two vaccinated foxes did not seroconvert and succumbed to rabies challenge.
* Raccoon dogs : protection in all vaccinated raccoon dogs.
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007
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Conclusion
- The square fishmeal polymer bait V-RG tested in domestic dogs, foxes and raccoon dogs was attractive, immunogenic and efficient.
- The efficacy data support the idea of a potential sourcing of this oral rabies vaccine :
• for oral vaccination campaigns in those European countries where both foxes and raccoon dogs represent major wildlife species affected by rabies,
• for oral vaccination of dogs as a complement to other means (parenteral vaccination and ABC programs) in countries where canine rabies is endemic.
Towards the elimination of rabies in Eurasia, Paris, 27-30 May 2007
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ACKNOWLEDGMENTS
- Chuck Rupprecht (CDC)
- Jacqueline Bailly, Michel Munier, Nicolas Penel, Josiane Ambert, Jean-Michel Bousset, Audrey Hamen, Michel Ritleng, Chantal Patron, Patricia Grosgeorge, Anouck Labadie, Estelle Litaize and Sébastien Kempff and Jean Luc Schereffer (AFSSA Nancy)
