An approach to local immunotoxicity induced by adjuvanted vaccines

Batista-Duharte, Alexander; Portuondo, Deivys Leandro; Carlos, Iracilda Zeppone; Pérez, Óliver

doi:10.1016/j.intimp.2013.07.025

Cited by 24 publications

(34 citation statements)

References 120 publications

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“…Each used vaccine in this study differed in its composition. This assumption is confirmed by human studies which displayed different local reactions caused by different adjuvants (Batista-Duharte et al, 2013;Edelman, 1980;Gupta et al, 1993).…”

Section: Discussionsupporting

confidence: 55%

Safety testing of veterinary vaccines using magnetic resonance imaging in pigs

Bernau

Kremer

Pappenberger

et al. 2015

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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.

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Section: Discussionsupporting

confidence: 55%

Safety testing of veterinary vaccines using magnetic resonance imaging in pigs

Bernau

Kremer

Pappenberger

et al. 2015

ALTEX

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“…In human medicine magnetic resonance imaging (MRI) is an approved method for diagnosis and follow-up of musculoskeletal diseases (Kuo and Carrino, 2007;Messineo et al, 1998;Schedel et al, 1992;Walker, 2008;Young and Bydder, 2003). MRI has been used in mice to evaluate antigen clearance after vaccination (Brewer et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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

Bernau

Kremer

Kreuzer

et al. 2016

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SummaryThe 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.

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“…174 The scientific literature contains reports of several hundred adjuvants with efficacy profiles that could be better than most adjuvants that currently approved for use in licensed vaccines, but none of these are clinically relevant because of their unsatisfactory safety profiles. 12,100 From this perspective, the potential of LVA for use in human vaccines is supported by evidence from the preclinical and clinical studies and a compelling safety profile. In the most recent published study, LVA doses equivalent to those shown to be immunogenic in mice were tolerable in humans and did not appear to cause any skin damage.…”

Section: Discussionmentioning

confidence: 99%

“…99 Unfortunately, this persistence of inflammatory signaling may also play a role in diminishing the safety of these adjuvants. 12,100 LVAs appear to function quite distinctly from chemical adjuvants in that they result in tissue signaling and the activation of APCs, but do not appear to trigger significant inflammatory responses. Chen et al reported that the activation and migration of APCs in the skin following 532 nm Q-Nd:YAG laser treatment was not accompanied by a significant increase in inflammatory cytokines including TNF-α, IL-1β, IL-6, and CCL2.…”

mentioning

confidence: 99%