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Noël TORDO

CANINE ADENOVIRUS-BASED VACCINES AGAINST RABIES. Noël TORDO. working together to stop the ongoing tragedy of rabies!. Institut Pasteur, Paris, France Unit Antiviral Strategies Corinne JALLET Noël TORDO INRA-AFSSA-ENVA Maisons-Alfort, France UMR1161 - Virologie Marion SZELECHOWSKI

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Noël TORDO

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  1. CANINE ADENOVIRUS-BASED VACCINES AGAINST RABIES Noël TORDO working together to stop the ongoing tragedy of rabies!

  2. Institut Pasteur, Paris, France Unit Antiviral Strategies Corinne JALLET Noël TORDO INRA-AFSSA-ENVAMaisons-Alfort, France UMR1161 - Virologie Marion SZELECHOWSKI Annie FOURNIER Bernard KLONJKOWSKI Marc ELOIT

  3. previous papers…

  4. Recombinant canine adenovirus (Cav2) right ITR left ITR Wild-type Cav2 E1+ E3+ Replicative Cav2 Cav-G R+ G PV E1+ E3+ Non Replic. Cav2 Cav-G R0 G PV E3+ E10 Non Replic. Human Ad5-G R0 G PV E10 E30 Replicative Cav2 Cav-GFP R+ GFP E1+ E3+

  5. Expression of recombinant Gpv in CHO-CAR cells (24h; 10 TCID50) Ad5 G R0 purif.G M Cav2 NI Cav2 G R0 Cav2 G R+ Western blot Polyclonal G4846 Cav2-G R+ Ad5-G R0 Cav2 Cav2-G R0 IF MAb G D1 Cav-G R+ Ad5-G R0 Cav-G R0 Cav2 99.51 % 1162.35 Flow cytometry MAb G D1 99.51 % 1162.35 92.44 % 396 95.68 % 531.80 2.08 % 21.26

  6. DK DK-E1 Cav2-G R+ Cav2 10 10 10 10 Cav2-G R+ 10 9 10 9 Cav2 10 8 10 8 Cav2-GFP R+ 10 7 10 7 Cav2-GFP R+ 10 6 10 6 10 5 10 5 Total Infectious Units/ml Total Infectious Units/ml 10 4 10 4 10 3 10 3 10 2 10 2 10 1 10 1 10 0 10 0 0 24 48 72 96 0 24 48 72 96 Hours DK Hours 10 10 10 9 DK-E1 10 8 10 7 10 6 CRFK 10 5 Total Infectious Units/ml 10 4 10 3 293 10 2 10 1 10 0 0 24 48 72 96 Hours Multiplication of CaV2-derived viruses in various cell lignes (MOI = 1) dog cells Cav2 other cells

  7. Immunogenicity of recombinant Cav2in C57BL/6 mice by IM route (107 TCID50) • I.M. immunization (tibialis muscle) • 107 TCID50Cav2 in 50 ml / mouse • 27 day (VNAbs) • 48 days (VNAbs + T cell response)

  8. Immunogenicity of recombinant Cav2by IM route (107 TCID50)individual results Virus Neutralizing Antibodies (VNA) Proliferative Index (G protein) Ad5-G R0 Cav-G R0 Cav-G R+ Cav2 Ad5-G R0 Cav-G R0 Cav-G R+ Cav2

  9. Immunogenicity of recombinant Cav2by IM route (107 TCID50) Virus Neutralizing Antibodies (VNA) Proliferative Index (G protein)

  10. Protection of recombinant Cav2IM (7.106 TCID50) or oral (7.107 TCID50) routes • 21 day (VNAbs) • 25 day (challenge) 7.106 TCID50 7.107 TCID50

  11. Protection of recombinant Cav2IM (7.106 TCID50) or oral (7.107 TCID50) routes Virus Neutralizing Antibodies (day 21) Challenge (day 25) IM Cav-G R+ OR Cav-G R+ IM Cav-GFP R+ OR Cav-GFP R+ Control

  12. Experiments in dogs in progress… Collaboration with the AFSSA Nancy Florence CLIQUET Jacques BARRAT

  13. Cav2 grow well in canine cell lines and produce significant quantities of recombinant rabies G protein • Canine adenovirus (Cav2) -derived viruses (replicative and non replicative) expressing the rabies (PV strain) G protein have been produced • Cav2 are immunogenic (humoral and cellular responses) by both IM and oral routes • Dog experiments are in progress… • IM and oral vaccination of mice with replicative Cav2 G viruses protect them against a peripheral challenge • . • . • . • . • . CONCLUSIONS Cav2 G viruses are promising tools for oral vaccination of dogs

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