Presentation on theme: "Academy of Military Medical Science"— Presentation transcript:
1 Academy of Military Medical Science Vaccination of dogs using a recombinant canine adenovirus type-2 viral vector confers long-lasting immunity against rabiesVeterinary InstituteAcademy of Military Medical ScienceChangchun, Jilin, China28 May, 2007Paris
2 Human rabies in China in the most recent decade 159222229343495891119120372651254832155001000150020002500300035001996199719981999200220032004200520062001YearHuman rabies in China in the most recent decadeHuman rabies cases geological distribution in China
3 Rabies reservoir or vectors in China Dogs: 98%Cats: 4-5%Badger: 15 cases were reportedRats: in some areas in the south of ChinaFoxes: Inner MongoliaWolves: XinjiangBats:?
4 Vaccines for dogs in China ERA: in five combined vaccinesFlury LEP: approved for two yearsInactivated (imported) : Intervet, Merial,Fort DodgeInactivated (home-made): 3-4 types, inclinical 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 SAG1SAG2reverse genetically modified……Recombinant live virus vectorPoxvirus-vector basedAdenovirus-vector based
6 Advantages of adenovirus SafeWide range of hostHeat stable (Oral infection)Median package of a foreign genePersistent existence ?
7 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:Patent1:Patent2:Non-essential for replicationForeign gene or label insertsFiberpIX
8 Strategies for recombinant virus construction Homologous recombinationGene cloning
9 Our constructs Glycoprotein: SRV9 CVS-24 8202(street strain) Nucleoprotein:The recombinant CAV-2 genome containing the rabies virus glycoprotein expression cassette in plasmid form
10 Production of the recombinant virus MDCK cellsCPEWestern blotanalysisHandling of canine adenovirus (safe)MDCK easy grownObvious CPEHigh titer: around 10(8.5)
11 Bait composition Five parts: the recombinant virus solution; pledget; tallow; metal frame;paper package
13 Vaccination and antibody induction in dogs Inoculation routesTotal No. dogsTake the baitsor vaccinatedDevelop neutralizing antibodyAntibody last for 2 years at a protective levelBait(oral)9690/9679/90 (87.8%)72/90(80.0%)Solution (intranasal)4646/4640/46 (87.0%)36/46(78.3%)
15 Challenge results of dogs orally vaccinated and the negative controls GroupsNumber of dogs died after different time of vaccinationDogs survived1 week2 weeks3 weeks4 weeks5 weeksOrally vaccinated10Negative control631