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)

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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

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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.

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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

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Travel destinations (all animals)

EU 12%

Sweden / Norway 55%

UK 20%

n.k.13%

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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

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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

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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

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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

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Overall compliance of regulations

72%

15%

13%yes

no

n.k.

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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

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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