Vaccine safety testing using magnetic resonance imaging in suckling pigs

Abstract

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.

Detection of Local Tissue Reactions after Anti-GnRF Injection in Male Pigs Assessed Using Magnetic Resonance Imaging

“…Injection of the immunologic product results in local tissue reactions detectable by MRI, which is confirmed in previous studies dealing with MRI as an alternative method for safety testing [25,27]. MRI offers a three-dimensional repetitive monitoring of local reaction sizes in vivo in animals of different age and weight groups [24][25][26][27].…”

“…McGlone et al [42] did not find any reaction at the injection site although it was reported that cellular damage away from the injection site can be induced [43]. It was proven, that MRI can detect local tissue reactions [24][25][26][27], which was confirmed by pathomorphological examination [25,27] although in most cases no macroscopic tissue changes were detected on the skin surface. Therefore, to evaluate local tissue reactions, palpation of the injection site and macroscopic skin observations may not show their full extent.…”

“…Alterations with an increased signal intensity in T1-weighted MR images can represent inflammatory tissue, fatty infiltration or hematoma [30,31]. Signal intensity changes post injection can be traced back to inflammatory reactions [25,27] and especially in later progress to fibrotic changes like fatty infiltration (data not published). This is confirmed by pathomorphological examination in previous studies of pigs of different ages and weights [25,27].…”

“…Signal intensity changes post injection can be traced back to inflammatory reactions [25,27] and especially in later progress to fibrotic changes like fatty infiltration (data not published). This is confirmed by pathomorphological examination in previous studies of pigs of different ages and weights [25,27]. All regions in the present study showing increased signal intensities in T1-weighted images were traced back to inflammatory reactions due to the injection.…”

“…MRI allows the detection of various conditions like trauma, infection or inflammation. In animals, MRI can be used to detect antigen clearance or in pharmacological research [21][22][23][24][25][26][27].…”