Development of a preclinical humanized mouse model to evaluate acute toxicity of an influenza vaccine.

Development of a preclinical humanized mouse model to evaluate acute toxicity of an influenza vaccine. Oncotarget. 2018 May 25;9(40):25751-25763 Authors: Sasaki E, Momose H, Hiradate Y, Furuhata K, Mizukami T, Hamaguchi I Abstract Safety evaluation of a human vaccine is critical for vaccine development and for preventing an unexpected adverse reaction in humans. Nonetheless, to date, very few systems have been described for preclinical studies of human adverse reactions in vivo. Previously, we have identified biomarker genes expressed in the lungs for evaluation of influenza vaccine safety, and their usefulness in rodent models and for adjuvant-containing vaccines has already been reported. Here, our purpose was to develop a novel humanized mouse model retaining human innate-immunity-related cells to assess the safety of influenza vaccines using the previously identified biomarker genes. In the present study, we tested whether the two humanized models, a short-term and long-term reconstitution model of NOD/Shi-scid IL2rĪ³null mice, are suitable for biomarker gene-based safety evaluation. In the short-term model, human CD14+ cells, plasmacytoid dendritic cells, CD4+ and CD8+ T cells, and B cells were retained in the lungs. Among these cells, human CD14+ cells and plasmacytoid dendritic cells were not detected in the lungs of the long-term model. After the vaccination, the expression levels of human biomarker genes were elevated only i...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research