7 Hu dogs

Vaccination of dogs using a recombinant canine adenovirus type-2 viral vector confers long-lasting immunity against rabies: 

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

Rabies reservoir or vectors in China: 

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: 

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: 

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: 

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

Adenovirus: 

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 replication Foreign gene or label inserts Adenovirus

Strategies for recombinant virus construction: 

Strategies for recombinant virus construction Homologous recombination Gene cloning

Our constructs: 

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: 

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: 

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

Slide12: 

Bait uptake

Vaccination and antibody induction in dogs: 

Vaccination and antibody induction in dogs

Antibody production and persistence: 

Antibody production and persistence

Challenge results of dogs orally vaccinated and the negative controls: 

Challenge results of dogs orally vaccinated and the negative controls

Prospect: 

Prospect In cats In pigs In cattle and more Dogs Bats

Conclusions: 

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