Vaccine safety testing using magnetic resonance imaging in suckling pigs.

Safety testing is one major part of the licensing procedure for veterinary vaccines and demands a large number of animals. Magnetic resonance imaging (MRI) was tested as an alternative, which may lead to a reduction in numbers of animals required for safety testing, and, correspondingly to a detailed description of the three-dimensional extent of the local tissue reaction repetitively in live pigs. In previous pig studies the following questions arose:To answer these questions the following study was performed by comparing two vaccine groups of suckling piglets (8 animals per group; A and B) with two control groups (4 animals per group; C and D). One control group was injected with a saline solution (C) and the other was only tattoo marked (D). The animals were examined using MRI at days 1, 8, 15, 22, 29, 36, and 43 post vaccination, ending with a final pathomorphologic examination. Pathomorphologic examination confirmed MRI findings. Saline solution does not result in a local tissue reaction as detected after injecting vaccines. Tattoo marking causes no local tissue reaction, neither in MRI nor in pathomorphologic examination. Therefore, MRI can be used as an alternative method for safety testing of vaccines in pigs of different age categories offering repetitive measurements of local tissue reactions. Involved cells might be examined only in a final pathomorphologic examination at the end of the trial on a reduced number of animals.

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.