Immunosafety evaluation in Juvenile Göttingen Minipigs
Although an extrapolation from the clinical experience in adults can often be considered to support the pediatric use for most pharmaceutical compounds, differences in safety profiles between adult and pediatric patients can be observed. The developing immune system may be affected due to exaggerate...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Immunotoxicology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/1547691X.2022.2088904 |
| _version_ | 1818242473829335040 |
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| author | Linda Allais Alicia Perbet Fabienne Condevaux Jean-Paul Briffaux Marc Pallardy |
| author_facet | Linda Allais Alicia Perbet Fabienne Condevaux Jean-Paul Briffaux Marc Pallardy |
| author_sort | Linda Allais |
| collection | DOAJ |
| description | Although an extrapolation from the clinical experience in adults can often be considered to support the pediatric use for most pharmaceutical compounds, differences in safety profiles between adult and pediatric patients can be observed. The developing immune system may be affected due to exaggerated pharmacological or non-expected effects of a new drug. Toxicology studies in juvenile animals could therefore be required to better evaluate the safety profile of any new pharmaceutical compound targeting the pediatric population. The Göttingen minipig is now considered a useful non-rodent species for non-clinical safety testing of human pharmaceuticals. However, knowledge on the developing immune system in juvenile minipigs is still limited. The objective of the work reported here was to evaluate across-age proportions of main immune cells circulating in blood or residing in lymphoid organs (thymus, spleen, lymph nodes) in Göttingen Minipigs. In parallel, the main immune cell populations from healthy and immunocompromised piglets were compared following treatment with cyclosporin A (CsA) at 10 mg/kg/day for 4 wk until weaning. The study also assessed functionality of immune responses using an in-vivo model after “Keyhole limpet hemocyanin” (KLH) immunization and an ex-vivo lymph proliferation assay after stimulation with Concanavalin A. The results demonstrated variations across age in circulating immune cell populations including CD21+ B-cells, αβ-T- and γδ-T-cells, NK cells, and monocytes. CsA-induced changes in immune functions were only partially recovered by 5 mo after the end of treatment, whereas the immune cell populations affected by the treatment returned to normal levels in animals of the same age. Taken together, the study here shows that in this model, the immune function endpoints were more sensitive than the immunophenotyping endpoints. |
| first_indexed | 2024-12-12T13:45:48Z |
| format | Article |
| id | doaj.art-791ac427c2544ba5a394ee9ffe37d225 |
| institution | Directory Open Access Journal |
| issn | 1547-691X 1547-6901 |
| language | English |
| last_indexed | 2024-12-12T13:45:48Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Immunotoxicology |
| spelling | doaj.art-791ac427c2544ba5a394ee9ffe37d2252022-12-22T00:22:41ZengTaylor & Francis GroupJournal of Immunotoxicology1547-691X1547-69012022-12-01191415210.1080/1547691X.2022.2088904Immunosafety evaluation in Juvenile Göttingen MinipigsLinda Allais0Alicia Perbet1Fabienne Condevaux2Jean-Paul Briffaux3Marc Pallardy4Charles River Laboratories France Safety Assessment, Saint-Germain-Nuelles, FranceCharles River Laboratories France Safety Assessment, Saint-Germain-Nuelles, FranceCharles River Laboratories France Safety Assessment, Saint-Germain-Nuelles, FranceCharles River Laboratories France Safety Assessment, Saint-Germain-Nuelles, FranceInserm, Inflammation, Microbiome, and Immunosurveillance, Université Paris-Saclay, Châtenay-Malabry, FranceAlthough an extrapolation from the clinical experience in adults can often be considered to support the pediatric use for most pharmaceutical compounds, differences in safety profiles between adult and pediatric patients can be observed. The developing immune system may be affected due to exaggerated pharmacological or non-expected effects of a new drug. Toxicology studies in juvenile animals could therefore be required to better evaluate the safety profile of any new pharmaceutical compound targeting the pediatric population. The Göttingen minipig is now considered a useful non-rodent species for non-clinical safety testing of human pharmaceuticals. However, knowledge on the developing immune system in juvenile minipigs is still limited. The objective of the work reported here was to evaluate across-age proportions of main immune cells circulating in blood or residing in lymphoid organs (thymus, spleen, lymph nodes) in Göttingen Minipigs. In parallel, the main immune cell populations from healthy and immunocompromised piglets were compared following treatment with cyclosporin A (CsA) at 10 mg/kg/day for 4 wk until weaning. The study also assessed functionality of immune responses using an in-vivo model after “Keyhole limpet hemocyanin” (KLH) immunization and an ex-vivo lymph proliferation assay after stimulation with Concanavalin A. The results demonstrated variations across age in circulating immune cell populations including CD21+ B-cells, αβ-T- and γδ-T-cells, NK cells, and monocytes. CsA-induced changes in immune functions were only partially recovered by 5 mo after the end of treatment, whereas the immune cell populations affected by the treatment returned to normal levels in animals of the same age. Taken together, the study here shows that in this model, the immune function endpoints were more sensitive than the immunophenotyping endpoints.https://www.tandfonline.com/doi/10.1080/1547691X.2022.2088904Developing immune systemjuvenileGöttingen minipigimmunotoxicology |
| spellingShingle | Linda Allais Alicia Perbet Fabienne Condevaux Jean-Paul Briffaux Marc Pallardy Immunosafety evaluation in Juvenile Göttingen Minipigs Journal of Immunotoxicology Developing immune system juvenile Göttingen minipig immunotoxicology |
| title | Immunosafety evaluation in Juvenile Göttingen Minipigs |
| title_full | Immunosafety evaluation in Juvenile Göttingen Minipigs |
| title_fullStr | Immunosafety evaluation in Juvenile Göttingen Minipigs |
| title_full_unstemmed | Immunosafety evaluation in Juvenile Göttingen Minipigs |
| title_short | Immunosafety evaluation in Juvenile Göttingen Minipigs |
| title_sort | immunosafety evaluation in juvenile gottingen minipigs |
| topic | Developing immune system juvenile Göttingen minipig immunotoxicology |
| url | https://www.tandfonline.com/doi/10.1080/1547691X.2022.2088904 |
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