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Verena Jakel
Institute of Virology Justus-Liebig-University Giessen
Federal agency for sera and vaccines
FACTORS INFLUENCING THE ANTIBODY
RESPONSE TO RABIES VACCINATION
V.Jakel1
K.Cussler2, M.König1, H.-J.Thiel1
1Institute of Virology, Justus-Liebig-Universität Giessen, Germany
2Paul-Ehrlich-Institut, Langen, Germany
Verena Jakel
Introduction
Dogs and cats vaccinated against rabies according to recommendations of manufacturer may fail to reach the titre of 0,5 IU/ml required for travel purposes
Cliquet, 2003: 7,4% dogs 1,9% cats Mansfield, 2004: 5,2% dogs 2,7% cats (lab 1)
4,1% dogs 2,9% cats (lab 2)
Survey Paul-Ehrlich-Institut, 2004: 10-18% dogs 0-5% cats (lab 1 – 3)
Verena Jakel
Material and Methods
Sera tested by FAVN assay Questionnaire sent to veterinarians of dogs and
cats tested for travel purposes Separate data query for animals with test result <
0,5 IU/ml („test failed“) and ≥ 0,5 IU/ml („test passed“)
< 0,5 IU/ml ≥ 0,5 IU/ml ∑
Dogs 1375 489 1864
Cats 19 74 93
Verena Jakel
Primovaccinated dogs have a 6-fold higher risk for test failure than multivaccinated dogs.
Influences on test result I: previous vaccinations
dogs cats
OR 6.52, p<0.0001, 95%-CI: 4.9 – 8.7
OR 8.49, p=0.0019, 95%-CI: 2.2 – 32.8
26,1
39,9
6,8
14,9
9,7 20,2
12,1 12,7
45,2
12,30%
100%
< 0,5 IU/ ml ≥ 0,5 IU/ ml
1 2 3 > 3 n.k.
15,8
29,7
6,814,9
10,5 18,9
29,7
73,7
0%
100%
< 0,5 IU/ ml ≥ 0,5 IU/ ml
1 2 3 > 3 n.k.
Verena Jakel
Primovaccinated dogs tested more than 120 days after vaccination have a 3,27 fold higher risk for test failure than dogs tested during the first four months after vaccination
Influences on test result II (dogs): time vaccination - blood sampling
< 0,5 IU/ ml
26,4 21,5
47,1 49,1
26,5 29,4
0%
100%
Primo-vaccinated
Multi-vaccinated
Perc
enta
ge
0 - <120 120 - 240 > 240
≥ 0,5 IU/ ml
43,3 46,1
43,3 32,4
13,3 21,5
0%
100%
Primo-vaccinated
Multi-vaccinated
Perc
enta
ge
0 - <120 120 - 240 > 240
Verena Jakel
Travel destinations (all animals)
EU 12%
Sweden / Norway 55%
UK 20%
n.k.13%
Verena Jakel
Influences on test result III (dogs): Vaccine 4 different rabies virus strains for inactivated
vaccines in use in Germany
28,7 45,3
13,618
44,431,4
13,3 5,30%
100%
< 0,5 IU/ ml ≥ 0,5 IU/ ml
Per
cent
age
Vaccine strain No. 4
Vaccine strain No. 3
Vaccine strain No. 2
Vaccine strain No. 1
Verena Jakel
Influences on test result III (dogs): Vaccine
Vaccine strain OR 95%-CI P*-value
1 2 3.923 2.519 6.110 <0.0001
1 3 3.311 2.042 5.369 <0.0001
4 2 2.230 1.750 2.841 <0.0001
4 3 1.882 1.380 2.565 <0.0001
4 1 1.761 1.125 2.755 0.0134
3 2 1.185 0.875 1.604 0.2725*αi Bonferroni-Holm adjusted for multiple tests
Dogs vaccinated with vaccine strains 2 or 3 have a lower risk for test failure than dogs vaccinated with vaccine strain 1 or 4
Verena Jakel
Influences on test result IV (dogs): Vaccine
Dogs vaccinated with monovalent vaccines have a lower risk for test failure (OR 0.662, 95%-CI: 0.552 - 0.840, p=0.0007)
20,327,9
78,771,6
0
100
<0.50 ≥0.50
Per
cent
age
monovalent
polyvalent
Verena Jakel
Summary
Significant influence on test outcome: Number of rabies vaccinations animal has received in
lifetime Time between vaccination and blood sampling Strain of rabies vaccine Vaccine formulation
No significant influence on test outcome: Sex Medical treatment in parallel to rabies vaccination
Travel regulations frequently not complied
Verena Jakel
Overall compliance of regulations
72%
15%
13%yes
no
n.k.
Verena Jakel
Conclusions
Booster vaccination necessary in dogs and young cats to enhance probability of test result of ≥ 0,5 IU/ml
Significant differences between vaccines to induce rabies virus neutralizing antibodies
Harmonization of regulations for better compliance compulsory
Verena Jakel
Outlook
Additional statistical analysis of data on influence of vaccination history and vaccines
Influence of test virus strain (CVS) and vaccine strains on FAVN results
Verena Jakel
C. Förster M. Lenhard S. Deike B. Bank-Wolf Dr. D. Chauvet
Institute of Virology Justus-Liebig-University Giessen
Acknowledgements
PD Dr. A. Hoffmann
Dr. A. Mergel
The study was financially supported by the Federal Ministry of Food, Agriculture and Consumer Protection (BMVEL), Germany
Federal agency for sera and vaccines