Vaccination of dogs using a recombinant canine adenovirus type-2 viral vector confers long-lasting immunity against rabies...
Human rabies in China in the most recent decade Human rabies cases geological distribution in China 159 222 229 343 495 89...
Rabies reservoir or vectors in China <ul><li>Dogs: 98% </li></ul><ul><li>Cats: 4-5% </li></ul><ul><li>Badger: 15 cases wer...
Vaccines for dogs in China <ul><li>ERA:  in five combined vaccines </li></ul><ul><li>Flury LEP:  approved for two years </...
Oral vaccines for dogs <ul><li>Attenuated or mutated live rabies virus </li></ul><ul><li>SAD-B19 </li></ul><ul><li>SAG1 </...
Advantages of adenovirus <ul><li>Safe </li></ul><ul><li>Wide range of host </li></ul><ul><li>Heat stable (Oral infection) ...
<ul><li>Hu RL et al. Microbes  Infect, 2006, 8(4): 1090-1097   </li></ul><ul><li>Liu Y, Hu R, Zhang S, et al Viral Immunol...
Strategies for recombinant virus construction <ul><li>Homologous recombination </li></ul><ul><li>Gene cloning </li></ul>
Our constructs The recombinant CAV-2 genome containing the rabies virus glycoprotein expression cassette in plasmid form  ...
Production of the recombinant virus <ul><li>Handling of canine adenovirus (safe) </li></ul><ul><li>MDCK easy grown </li></...
Bait composition Five parts:  the recombinant virus solution;  pledget; tallow; metal frame;  paper package
Bait uptake
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 (8...
Antibody production and persistence
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 vac...
Prospect <ul><li>In cats </li></ul><ul><li>In pigs </li></ul><ul><li>In cattle </li></ul><ul><li>and  more </li></ul>Dogs ...
Conclusions <ul><li>A new, safe and efficacious rabies vaccine </li></ul><ul><li>A simple and useful bait </li></ul><ul><l...
 
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Vaccination of dogs using a recombinant canine adenovirus ...

  1. 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. 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. 3. Rabies reservoir or vectors in China <ul><li>Dogs: 98% </li></ul><ul><li>Cats: 4-5% </li></ul><ul><li>Badger: 15 cases were reported </li></ul><ul><li>Rats: in some areas in the south of China </li></ul><ul><li>Foxes: Inner Mongolia </li></ul><ul><li>Wolves: Xinjiang </li></ul><ul><li>Bats:? </li></ul>
  4. 4. Vaccines for dogs in China <ul><li>ERA: in five combined vaccines </li></ul><ul><li>Flury LEP: approved for two years </li></ul><ul><li>Inactivated (imported) : Intervet, Merial, </li></ul><ul><li>Fort Dodge </li></ul><ul><li>Inactivated (home-made): 3-4 types, in </li></ul><ul><li>clinical trial, not yet approved </li></ul><ul><li>* Vaccination of inactivated vaccine in rural areas needs laborious work. </li></ul>
  5. 5. Oral vaccines for dogs <ul><li>Attenuated or mutated live rabies virus </li></ul><ul><li>SAD-B19 </li></ul><ul><li>SAG1 </li></ul><ul><li>SAG2 </li></ul><ul><li>reverse genetically modified </li></ul><ul><li>…… </li></ul><ul><li>Recombinant live virus vector </li></ul><ul><li>Poxvirus-vector based </li></ul><ul><li>Adenovirus-vector based </li></ul>
  6. 6. Advantages of adenovirus <ul><li>Safe </li></ul><ul><li>Wide range of host </li></ul><ul><li>Heat stable (Oral infection) </li></ul><ul><li>Median package of a foreign gene </li></ul><ul><li>Persistent existence ? </li></ul>
  7. 7. <ul><li>Hu RL et al. Microbes Infect, 2006, 8(4): 1090-1097 </li></ul><ul><li>Liu Y, Hu R, Zhang S, et al Viral Immunology, 2006(19), 2:202-209 </li></ul><ul><li>Patent1: </li></ul><ul><li>20041001097.8 </li></ul><ul><li>Patent2: </li></ul><ul><li>20041001200.3 </li></ul><ul><li>Non-essential for replication </li></ul><ul><li>Foreign gene or label inserts </li></ul>Adenovirus Fiber pIX
  8. 8. Strategies for recombinant virus construction <ul><li>Homologous recombination </li></ul><ul><li>Gene cloning </li></ul>
  9. 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. 10. Production of the recombinant virus <ul><li>Handling of canine adenovirus (safe) </li></ul><ul><li>MDCK easy grown </li></ul><ul><li>Obvious CPE </li></ul><ul><li>High titer: around 10(8.5) </li></ul>MDCK cells CPE Western blot analysis
  11. 11. Bait composition Five parts: the recombinant virus solution; pledget; tallow; metal frame; paper package
  12. 12. Bait uptake
  13. 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. 14. Antibody production and persistence
  15. 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. 16. Prospect <ul><li>In cats </li></ul><ul><li>In pigs </li></ul><ul><li>In cattle </li></ul><ul><li>and more </li></ul>Dogs Bats
  17. 17. Conclusions <ul><li>A new, safe and efficacious rabies vaccine </li></ul><ul><li>A simple and useful bait </li></ul><ul><li>For oral use </li></ul><ul><li>Long lasting immunization in dogs </li></ul>
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