Magnetic resonance imaging to detect local tissue reactions after vaccination in sheep in vivo

Abstract

ObjectivesVaccination is one of the most effective methods to keep up the health status in humans and in livestock. Therefore, farm animals are vaccinated several times during their lifetime. Although vaccines are being checked regarding their local reactogenicity, side effects occur frequently—especially in the case of the application of adjuvanted products. Many reports exist about local reactions in sheep. The present study aimed at testing MRI as a method to document injection site reactions three-dimensionally.DesignTwo groups of Merino lambs (n=16 each) were vaccinated subcutaneously into the left neck side. Two different, licensed inactivated vaccines were used. Both groups of lambs were anaesthetised and scanned using MRI at days 1, 3, 8, 15, 22 and 29 after vaccination.SettingThe study was performed on a commercial-like farm.ParticipantsThirty-two Merino lambs entered the experiment, 16 male and 16 female ones (one animal died at day 22 after vaccination). At first examination day they were approximately three months old.Primary and secondary outcome measuresVolume differences were measured between vaccination and control neck side to evaluate the time pattern of local tissue reactions.ResultsLocal tissue reactions were visible on the skin surface and also appeared in deeper tissue layers on MRI. These deeper reactions would not have been found without MRI or, alternatively, without sacrificing the animals. Some of these extensive local reactions lasted for more than 29 days.ConclusionsThe in vivo MRI results proved suitable to record local tissue reactions in terms of three-dimensional extent over a longer period of time in large farm animals without the need to sacrifice test animals. A three-dimensional MRI examination of the injection site during regulatory licensing studies offers an objective evaluation that could be used in a benefit-risk assessment of veterinary vaccines.Trial registration numberDistrict Government of Upper Bavaria:55.2-1-54-2532-2-13.

Evaluation of the AV7909 Anthrax Vaccine Toxicity in Sprague Dawley Rats Following Three Intramuscular Administrations

“…Furthermore, the 14-day recovery period, which is in line with current regulatory guidance for preclinical safety evaluation of vaccines, may not be sufficiently long to observe complete resolution of the local reactions. 29 Similar local reactogenicity observations were reported for other CpG ODN-adjuvanted vaccines, including those against hepatitis B, 30,31 influenza, 32 malaria, 33-35 pneumococcus, 36,37 cytomegalovirus, and tetanus. 38 Of note, in the recent repeat-dose toxicity study in juvenile rats, 27 AV7909 was also well tolerated with no severe adverse effects or morbidity and induced a strong neutralizing antibody response.…”

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

“…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.…”

“…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 ]. Alterations with an increased signal intensity in T1-weighted MR images can represent inflammatory tissue, fatty infiltration or hematoma [ 30 , 31 ].…”

“…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 ].…”

MRI/PET multimodal imaging of the innate immune response in skeletal muscle and draining lymph node post vaccination in rats

“…Indeed, Bernau et al. have successfully used MRI to assess local reaction for a number of veterinary vaccines in pigs and sheep ( 37 – 40 ). Additionally, MRI was used by Brewer et al.…”