Caracy

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

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previous papers
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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
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Expression of recombinant Gpv in CHO-CAR cells
(24h 10 TCID50)
Ad5 G R0
Cav2 G R
Cav2 G R0
Cav2
M
purif.G
NI
Western blot Polyclonal G4846
Ad5-G R0
Cav2-G R
Cav2
Cav2-G R0
IF MAb G D1
Ad5-G R0
Cav-G R
Cav-G R0
Cav2
99.51 1162.35
99.51 1162.35
Flow cytometry MAb G D1
92.44 396
95.68 531.80
2.08 21.26
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Multiplication of CaV2-derived viruses in
various cell lignes (MOI 1)
dog cells
Cav2
other cells
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Immunogenicity of recombinant Cav2 in C57BL/6
mice by IM route (107 TCID50 )

• I.M. immunization (tibialis muscle)
• 107 TCID50 Cav2 in 50 ml / mouse
• 27 day (VNAbs)
• 48 days (VNAbs T cell response)

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Immunogenicity of recombinant Cav2 by 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
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Immunogenicity of recombinant Cav2 by IM route
(107 TCID50 )
Virus Neutralizing Antibodies (VNA)
Proliferative Index (G protein)
D48 D48
Proliferative index Range
Ad5-G0 2,23 1,5-3
Cav-G R0 1,94 1,1-2,7
Cav-G R 1,98 1,7-4,6
Cav2 1
D27 D27 D48 D48
VNA GMT Range VNA GMT Range
Ad5-GR0 316,77 101-546 194,35 76-504
Cav-G R0 58,23 47,6-72,3 46,18 23,1-72,4
Cav-G R 56,33 44,2-68,9 68,27 52-78
Cav2 0 0
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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
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Protection of recombinant Cav2IM (7.106 TCID50 )
or oral (7.107 TCID50 ) routes
Virus Neutralizing Antibodies (day 21)
Challenge (day 25)
Vaccination Route VNA GMT (IU) Range Survivors
Cav-G R IM 45,28 25-83 9/9
Cav-G R oral 1,64 0,38-7,5 7/9
Cav-GFP R IM 0 0/5
Cav-GFP R oral 0 0/5
Control 0 0/3
IM Cav-G R
OR Cav-G R

IM Cav-GFP R
OR Cav-GFP R
Control
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Experiments in dogs in progress
Collaboration with the AFSSA Nancy Florence
CLIQUET Jacques BARRAT
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CONCLUSIONS
Cav2 G viruses are promising tools for oral
vaccination of dogs
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