Vaccination of dogs using a recombinant canine adenovirus ...
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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. Human rabies in China in the most recent decade Human rabies cases geological distribution in China 159 222 229 343 495 891 1191 2037 2651 2548 3215 0 500 1000 1500 2000 2500 3000 3500 1996 1997 1998 1999 2000 2002 2003 2004 2005 2006 2001 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): 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 Fiber pIX
  • 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-24 8202(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 36/46(78.3%) 40/46 (87.0%) 46/46 46 Solution (intranasal) 72/90(80.0%) 79/90 (87.8%) 90/96 96 Bait (oral) Antibody last for 2 years at a protective level Develop neutralizing antibody Take the baits or vaccinated Total No. dogs Inoculation routes
  • 14. Antibody production and persistence
  • 15. Challenge results of dogs orally vaccinated and the negative controls 1 0 0 3 6 0 Negative control 10 0 0 0 0 0 Orally vaccinated 5 weeks 4 weeks 3 weeks 2 weeks 1 week Dogs survived Number of dogs died after different time of vaccination Groups
  • 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
  • 18.