vaccination of dogs using a recombinant canine adenovirus
DESCRIPTION
TRANSCRIPT
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Vaccination of dogs using a recombinant canine adenovirus type-2 viral vector confers long-lasting immunity against rabies
Veterinary InstituteAcademy of Military Medical Science
Changchun, Jilin, China
28 May, 2007Paris
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Human rabies in
China in the most recent
decade
0
500
1000
1500
2000
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3000
3500
96 97 98 99 00 01 02 03 04 05 06Year
CasesseHuman
rabies cases geological
distribution in China
159 222 229343
495
891
1191
2037
26512548
3215
0
500
1000
1500
2000
2500
3000
3500
1996 1997 1998 1999 2000 2002 2003 2004 2005 20062001
Year
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Rabies reservoir or vectors in China
Dogs: 98%Cats: 4-5%Badger: 15 cases were reportedRats: in some areas in the south of
ChinaFoxes: Inner MongoliaWolves: XinjiangBats:?
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Vaccines for dogs in China
ERA: in five combined vaccinesFlury LEP: approved for two years Inactivated (imported) : Intervet, Merial,
Fort Dodge Inactivated (home-made): 3-4 types, in clinical trial, not yet approved* Vaccination of inactivated vaccine in rural
areas needs laborious work.
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Oral vaccines for dogs
▓ Attenuated or mutated live rabies virus SAD-B19 SAG1 SAG2 reverse genetically modified …… ▓ Recombinant live virus vector Poxvirus-vector based Adenovirus-vector based
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Advantages of adenovirus
Safe Wide range of host Heat stable (Oral infection) Median package of a foreign gene Persistent existence ?
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★ Hu RL et al. Microbes Infect, 2006, 8(4): 1090-1097
★ Liu Y, Hu R, Zhang S, et al Viral Immunology, 2006(19), 2:202-209
★ Patent1: 20041001097.8★ Patent2: 20041001200.3☆ Non-essential for replic
ation☆ Foreign gene or label ins
erts
FiberpIX
Adenovirus
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Strategies for recombinant virus construction
Homologous recombination
Gene cloning
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Our constructs
The recombinant CAV-2 genome containing the rabies virus glycoprotein expression cassette in plasmid form
Glycoprotein: SRV9 CVS-24 8202(street strain)Nucleoprotein: SRV9
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Production of the recombinant virus
◢ Handling of canine adenovirus (safe)
◢ MDCK easy grown
◢ Obvious CPE◢ High titer:
around 10(8.5)
MDCK cells
CPE
Western blotanalysis
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Bait composition
Five parts: the recombinant virus solution; pledget; tallow; metal frame; paper package
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Bait uptake
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Vaccination and antibody induction in dogs
Inoculation routes
Total No.
dogs
Take the baits
or vaccinated
Develop neutralizing
antibody
Antibody last for 2 years at a protective
level
Bait(oral)
96 90/96 79/90 (87.8%)
72/90(80.0%)
Solution (intranasa
l)
46 46/46 40/46 (87.0%)
36/46(78.3%)
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Antibody production and persistence
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Challenge results of dogs orally vaccinated and the negative
controls
Groups Number of dogs died after different time of vaccination
Dogs survived
1 week 2 weeks 3 weeks 4 weeks
5 weeks
Orally vaccinated
0 0 0 0 0 10
Negative control
0 6 3 0 0 1
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Prospect
♘ In cats♘ In pigs♘ In cattle♘ and more
DogsBats
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Conclusions
A new, safe and efficacious rabies vaccine
A simple and useful baitFor oral useLong lasting immunization in
dogs
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