Safety testing of veterinary vaccines using magnetic resonance imaging in pigs

Abstract

SummarySafety testing of veterinary vaccines requires the use of a large number of animals to investigate possible local and systemic reactions. This includes, among others, the pathological examination of the injection site in frequent intervals. This examination requires a selected killing of animals in frequent intervals. To reduce the number of animals needed for this kind of safety testing, magnetic resonance imaging (MRI) was used to detect and quantify possible local reactions after vaccination in vivo. Sixty-four pigs were divided into four experimental groups (n = 16); two groups consisting of 12-week-old pigs and two 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 MR images were evaluated semi-automatically, comparing the volumes of altered signal intensities on the vaccination side (VS) with the volumes of the signal intensities on 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 by scanning the same live animals at several time points after vaccination. MRI is a suitable alternative method for non-invasive safety testing of injectable medicines and can therefore be applied to reduce animal numbers used for safety testing purposes.

Retinal Organ Cultures as Alternative Research Models

“…46 Animals have been bred, used and killed for the purpose of investigating various pathological processes, as well as developing and testing drugs and therapies. 47,48 Glaucoma models, for example, have been established by experimentally inducing ocular hypertension, optic nerve crush or by injecting toxic agents resulting in ganglion cell death. [49][50][51][52][53] Retinal ischaemia is also regularly induced in animals for research purposes.…”

“…As porcine eyes are a by-product of the food industry, no animals have to be killed solely for research purposes. 48 An assessment of the survival of adult porcine neurosensory retinas was carried out by using 3-day retinal-RPE/ choroid co-cultures. 39 During research studies on RGCs, ex vivo cultures have been shown to remain viable for 7-10 days, which has facilitated the study of molecular mechanisms involved in disease.…”

“…As porcine eyes are a by-product of the food industry, no animals have to be killed solely for research purposes. 48…”

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

“…2007: ASC 3DDR-BN#07032 (FDA approved)) was used, in order to measure the local reaction. The volumes of regions with increased signal intensity at the vaccination side (VS) and at the control side (CS) were bordered semiautomatically at defined signal intensities on a grey scale level from 0 (black) -4096 (white) (Bernau et al, 2015). A region of interest (ROI) was created to cover the largest extent of the area with increased signal intensity at the VS.…”

“…Concerning muscle tissue, various alterations resulting from trauma, infection, inflammation or edema can be detected using MRI (Lovitt et al, 2006;May et al, 2000;Schrank et al, 2005;Shellock et al, 1996;Pathria and Boutin, 2009) due to signal intensity changes, especially when performing different protocols (T1-and T2-weightenings; see Hodgson, 2010;Pipe, 1999). Local reactions can be detected via MRI (Brewer et al, 2014;Rudin, 1994;Rudin et al, 1995) and results of our own study in pigs (Bernau et al, 2015) showed that MRI allows the documentation of local reactions after vaccination in the live pig, scanned repeatedly over 29 days.…”