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BackgroundThe pig is emerging as a model species that bridges the gap between rodents and humans in research. In particular, the miniature pig (referred to hereafter as the minipig) is increasingly being used as non-rodent species in pharmacological and toxicological studies. However, there is as yet a lack of validated behavioral tests for pigs, although there is evidence that the spatial holeboard task can be used to assess the working and reference memory of pigs. In the present study, we compared the learning performance of commercial pigs and Göttingen minipigs in a holeboard task.MethodsBiperiden, a muscarinic M1 receptor blocker, is used to induce impairments in cognitive function in animal research. The two groups of pigs were treated orally with increasing doses of biperiden (0.05 – 20 mg.kg-1) after they had reached asymptotic performance in the holeboard task.ResultsBoth the conventional pigs and the Göttingen minipigs learned the holeboard task, reaching nearly errorless asymptotic working and reference memory performance within approximately 100 acquisition trials. Biperiden treatment affected reference, but not working, memory, increasing trial duration and the latency to first hole visit at doses ≥ 5 mg.kg-1.ConclusionBoth pig breeds learned the holeboard task and had a comparable performance. Biperiden had only a minor effect on holeboard performance overall, and mainly on reference memory performance. The effectiveness needs to be evaluated further before definitive conclusions can be drawn about the ability of this potential cognition impairer in pigs.

Immunogenicity is a major issue of concern for monoclonal antibodies used in human diseases and is by default mainly determined in non-human primates (NHP), as target molecules are considered most similar in NHP compared to human. In this manuscript the predictive value of immunogenicity testing in minipigs for human safety is evaluated, as the immune system of the pig is functionally similar to that in other mammalian species. Adalimumab and infliximab (both monoclonal antibodies blocking TNFa) were used as model substances. Female Gö ttingen minipigs (4/group) were treated every other week with low (0.1 mg/kg), mid (1.0 mg/kg), or high dose (5 mg/kg) adalimumab or 5 mg/kg infliximab subcutaneous (SC) over a period of 8 weeks. After first and last dosing, pharmacokinetic analysis was performed. Anti-drug antibodies (ADAs) were measured on several time points. Furthermore, hematology, clinical chemistry, body weight, clinical signs, and histopathology of several organs were evaluated. No signs of toxicity of the treatments were observed in the limited organs and tissues collected. Eleven out of 12 minipigs treated with adalimumab elicited a detectable ADA response. Induction of ADA was correlated with decreased plasma levels of adalimumab. Infliximab clearance was comparable after first and last dose. Therefore, the presence of ADA directed to infliximab was considered highly unlikely. It was concluded that the minipig and NHP showed comparable suitability for immunogenicity prediction in humans. More studies with other biopharmaceutical products are needed to strengthen the status of the minipig as an alternative model for immunotoxicity testing including immunogenicity.

Histopathological examination of the nasal passages requires a standardized approach for recording lesion distribution patterns. Nasal diagrams provide guidance to map the lesions. Information on lesions exists for rodents, dogs, and monkeys, which all have been used in inhalation studies. Recently, minipigs have garnered interest as an inhalation model because minipigs resemble humans in many features of anatomy, physiology, and biochemistry and may be a good alternative to monkeys and dogs. The present work explored the microanatomy and histology of the nasal passages of Göttingen minipigs from postnatal day 1 until 6 months of age. Six nasal levels were selected, which allow examination of the squamous, transitional (nonciliated) and ciliated respiratory, and olfactory epithelia; the nasopharynx; and relevant structures such as the vomeronasal organ, olfactory bulb, and nasal/nasopharynx-associated lymphoid tissue.

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