vaccination of dogs using a recombinant canine adenovirus
DESCRIPTION
TRANSCRIPT
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
Human rabies in
China in the most recent
decade
0
500
1000
1500
2000
2500
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
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:?
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.
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
Advantages of adenovirus
Safe Wide range of host Heat stable (Oral infection) Median package of a foreign gene Persistent existence ?
★ 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
Strategies for recombinant virus construction
Homologous recombination
Gene cloning
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
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
Bait composition
Five parts: the recombinant virus solution; pledget; tallow; metal frame; paper package
Bait uptake
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%)
Antibody production and persistence
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
Prospect
♘ In cats♘ In pigs♘ In cattle♘ and more
DogsBats
Conclusions
A new, safe and efficacious rabies vaccine
A simple and useful baitFor oral useLong lasting immunization in
dogs