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Veterinary Institute Academy of Military Medical Science Changchun, Jilin, China 28 May, 2007

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. 3500. 3215. 3000. 2651. 2548. 2500. 2037. 2000. 1500. 1191.

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Veterinary Institute Academy of Military Medical Science Changchun, Jilin, China 28 May, 2007

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  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. 3500 3215 3000 2651 2548 2500 2037 2000 1500 1191 891 1000 495 500 343 229 222 159 0 1997 2002 2004 2005 1996 1998 1999 2000 2001 2003 2006 Year Human rabies in China in the most recent decade Human rabies cases geological distribution in China

  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): 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 pIX Fiber Adenovirus

  8. Strategies for recombinant virus construction • Homologous recombination • Gene cloning

  9. Our constructs Glycoprotein: SRV9 CVS-24 8202(street strain) Nucleoprotein: SRV9 The recombinant CAV-2 genome containing the rabies virus glycoprotein expression cassette in plasmid form

  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

  14. Antibody production and persistence

  15. Challenge results of dogs orally vaccinated and the negative controls

  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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