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:
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
Human rabies in China in the most recent decade Human rabies cases geological distribution in China Year
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:?
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.
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): 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
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 (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 blot analysis
Bait composition Five parts: the recombinant virus solution; pledget; tallow; metal frame; paper package
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%)
Antibody production and persistence
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
Prospect In cats In pigs In cattle and more Dogs Bats
Conclusions A new, safe and efficacious rabies vaccine A simple and useful bait For oral use Long lasting immunization in dogs