Institute of Virology JustusLiebigUniversity Giessen FACTORS INFLUENCING THE

Institute of Virology Justus-Liebig-University Giessen FACTORS INFLUENCING THE ANTIBODY RESPONSE TO RABIES VACCINATION V. Jakel 1 K. Cussler 2, M. König 1, H. -J. Thiel 1 1 Institute of Virology, Justus-Liebig-Universität Giessen, Germany 2 Paul-Ehrlich-Institut, Langen, Germany Verena Jakel Federal agency for sera and vaccines

Introduction p 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 p Cliquet, 2003: p Mansfield, 2004: 7, 4% dogs 1, 9% cats 5, 2% dogs 2, 7% cats (lab 1) 4, 1% dogs 2, 9% cats (lab 2) p Survey Paul-Ehrlich-Institut, 2004: 10 -18% dogs 0 -5% cats (lab 1 – 3) Verena Jakel

Material and Methods p Sera tested by FAVN assay p Questionnaire sent to veterinarians of dogs and cats tested for travel purposes p 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

Influences on test result I: previous vaccinations p Primovaccinated dogs have a 6 -fold higher risk for test failure than multivaccinated dogs OR 6. 52, p<0. 0001, 95%-CI: 4. 9 – 8. 7 cats Verena Jakel OR 8. 49, p=0. 0019, 95%CI: 2. 2 – 32. 8

Influences on test result II (dogs): time vaccination - blood sampling p 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 Verena Jakel

Travel destinations (all animals) Verena Jakel

Influences on test result III (dogs): Vaccine p 4 different rabies virus strains for inactivated vaccines in use in Germany Verena Jakel

Influences on test result III (dogs): Vaccine p Dogs vaccinated with vaccine strains 2 or 3 have a lower risk for test failure than dogs vaccinated with vaccine strain 1 or 4 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 Verena Jakel

Influences on test result IV (dogs): Vaccine p Dogs vaccinated with monovalent vaccines have a lower risk for test failure (OR 0. 662, 95%-CI: 0. 552 - 0. 840, p=0. 0007) Verena Jakel

Summary Significant influence on test outcome: p Number of rabies vaccinations animal has received in lifetime p Time between vaccination and blood sampling p Strain of rabies vaccine p Vaccine formulation No significant influence on test outcome: p Sex p Medical treatment in parallel to rabies vaccination Travel regulations frequently not complied Verena Jakel

Overall compliance of regulations Verena Jakel

Conclusions p Booster vaccination necessary in dogs and young cats to enhance probability of test result of ≥ 0, 5 IU/ml p Significant differences between vaccines to induce rabies virus neutralizing antibodies p Harmonization of regulations for better compliance compulsory Verena Jakel

Outlook p Additional statistical analysis of data on influence of vaccination history and vaccines p Influence of test virus strain (CVS) and vaccine strains on FAVN results Verena Jakel

Acknowledgements Institute of Virology Justus-Liebig-University Giessen Federal agency for sera and vaccines p C. Förster p M. Lenhard p S. Deike p B. Bank-Wolf p Dr. D. Chauvet p PD Dr. A. Hoffmann p Dr. A. Mergel p The study was financially supported by the Federal Ministry of Food, Agriculture and Consumer Protection (BMVEL), Germany Verena Jakel