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Vaccination of dogs using a recombinant canine adenovirus type-2 viral vector confers long-lasting immunity against rabies Veterinary Institute Academy.

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Presentation on theme: "Vaccination of dogs using a recombinant canine adenovirus type-2 viral vector confers long-lasting immunity against rabies Veterinary Institute Academy."— Presentation transcript:

1 Vaccination of dogs using a recombinant canine adenovirus type-2 viral vector confers long-lasting immunity against rabies Veterinary Institute Academy of Military Medical Science Changchun, Jilin, China 28 May, 2007 Paris

2 Human rabies in China in the most recent decade Human rabies cases geological distribution in China Year

3 Rabies reservoir or vectors in China Dogs: 98% Cats: 4-5% Badger: 15 cases were reported Rats: in some areas in the south of China Foxes: Inner Mongolia Wolves: Xinjiang Bats:?

4 Vaccines for dogs in China ERA: in five combined vaccines Flury 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.

5 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

6 Advantages of adenovirus Safe Wide range of host Heat stable (Oral infection) Median package of a foreign gene Persistent existence ?

7 Hu RL et al. Microbes Infect, 2006, 8(4): Liu Y, Hu R, Zhang S, et al Viral Immunology, 2006(19), 2: Patent1: Patent2: Non-essential for replication Foreign gene or label inserts Fiber pIX Adenovirus

8 Strategies for recombinant virus construction Homologous recombination Gene cloning

9 Our constructs The recombinant CAV-2 genome containing the rabies virus glycoprotein expression cassette in plasmid form Glycoprotein: SRV9 CVS (street strain) Nucleoprotein: SRV9

10 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 blot analysis

11 Bait composition Five parts: the recombinant virus solution; pledget; tallow; metal frame; paper package

12 Bait uptake

13 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) 9690/9679/90 (87.8%)72/90(80.0%) Solution (intranasal) 4646/4640/46 (87.0%)36/46(78.3%)

14 Antibody production and persistence

15 Challenge results of dogs orally vaccinated and the negative controls GroupsNumber of dogs died after different time of vaccination Dogs survived 1 week2 weeks3 weeks4 weeks5 weeks Orally vaccinated Negative control063001

16 Prospect In cats In pigs In cattle and more Dogs Bats

17 Conclusions A new, safe and efficacious rabies vaccine A simple and useful bait For oral use Long lasting immunization in dogs

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