Assessment of local reaction to vaccines in live piglets with magnetic resonance imaging compared to histopathology.

The safety of veterinary vaccines is assessed in clinical trials in Europe. The assessment of the local tissue reaction to vaccination by magnetic resonance imaging (MRI) could reduce the number of animals needed because repeated examinations can be performed in the same animal over time. The present study compared the evaluation of local tissue reactions to vaccination using MRI in live pigs with histopathology of porcine tissue, the current gold standard in regulatory safety testing. Eight piglets each were administered one of two commercial vaccines into marked injection sites. All animals were sedated and scanned repeatedly by MRI using a contrast agent up to day 29 after vaccination. On day 29, the animals were euthanized and underwent a pathological examination. The MRI results were compared with the pathomorphological findings at the injection site by regression analysis. The MR images and the pathological examinations yielded matching results concerning the sizes of the affected tissue volumes or areas. The use of MRI for regulatory safety testing can reduce the number of animals needed to 8 per examination group. The volume of a local reaction and its progression over time can be evaluated and documented. If persistent lesions develop a final pathomorphological examination is needed to identify the kind and local distribution of the reaction.

Safety testing of veterinary vaccines using magnetic resonance imaging in pigs.

Safety testing of veterinary vaccines requires the use of a large number of animals to investigate possible local and systemic reactions. This includes amongst others the pathological examination of the injection site in frequent intervals. For this a selected killing of animals in frequent intervals is inevitable. To reduce the number of animals needed for this kind of safety testing, magnetic resonance imaging (MRI) was used to detect and quantify possible inflammatory reactions after vaccination in vivo. Sixty four pigs were subdivided into 4 experimental groups (n=16); two groups consisting of 12 weeks old pigs and 2 of 6 month old pigs at vaccination day. The pigs were vaccinated with four licensed products (each group receiving one vaccine) and examined up to 6 times using MRI during a period of 5 weeks. The MRI images were evaluated semi-automatically comparing the volumes of altered signal intensities at the vaccination side (VS) with the volumes of the signal intensities at the control side (CS). A paired t-Test was used to identify significant differences (p<0.05) between VS and CS. The results show that MRI allows a 3D-quantification of the extent of local reactions in vivo, scanning the same animals at several points of time after vaccination. MRI is a suitable alternative method for non-invasive safety testing of injectable medicines and can therefore be used as an alternative method to reduce animal numbers for safety testing purposes.