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

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...

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Autores principales: Sasaki, Eita, Momose, Haruka, Hiradate, Yuki, Furuhata, Keiko, Mizukami, Takuo, Hamaguchi, Isao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995229/
https://www.ncbi.nlm.nih.gov/pubmed/29899819
http://dx.doi.org/10.18632/oncotarget.25399
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author Sasaki, Eita
Momose, Haruka
Hiradate, Yuki
Furuhata, Keiko
Mizukami, Takuo
Hamaguchi, Isao
author_facet Sasaki, Eita
Momose, Haruka
Hiradate, Yuki
Furuhata, Keiko
Mizukami, Takuo
Hamaguchi, Isao
author_sort Sasaki, Eita
collection PubMed
description 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 IL2rγ(null) 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 in the short-term model when the toxicity reference vaccine was inoculated. This phenomenon was not observed in the long-term model. The levels of human cytokines and chemokines in the lungs increased in response to the toxicity reference vaccine in the short-term mouse model. According to these results, the short-term model provides a better platform for evaluating vaccine safety in terms of human peripheral blood mononuclear cell–mediated initial reactions in vivo.
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spelling pubmed-59952292018-06-13 Development of a preclinical humanized mouse model to evaluate acute toxicity of an influenza vaccine Sasaki, Eita Momose, Haruka Hiradate, Yuki Furuhata, Keiko Mizukami, Takuo Hamaguchi, Isao Oncotarget Research Paper: Immunology 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 IL2rγ(null) 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 in the short-term model when the toxicity reference vaccine was inoculated. This phenomenon was not observed in the long-term model. The levels of human cytokines and chemokines in the lungs increased in response to the toxicity reference vaccine in the short-term mouse model. According to these results, the short-term model provides a better platform for evaluating vaccine safety in terms of human peripheral blood mononuclear cell–mediated initial reactions in vivo. Impact Journals LLC 2018-05-25 /pmc/articles/PMC5995229/ /pubmed/29899819 http://dx.doi.org/10.18632/oncotarget.25399 Text en Copyright: © 2018 Sasaki et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper: Immunology
Sasaki, Eita
Momose, Haruka
Hiradate, Yuki
Furuhata, Keiko
Mizukami, Takuo
Hamaguchi, Isao
Development of a preclinical humanized mouse model to evaluate acute toxicity of an influenza vaccine
title Development of a preclinical humanized mouse model to evaluate acute toxicity of an influenza vaccine
title_full Development of a preclinical humanized mouse model to evaluate acute toxicity of an influenza vaccine
title_fullStr Development of a preclinical humanized mouse model to evaluate acute toxicity of an influenza vaccine
title_full_unstemmed Development of a preclinical humanized mouse model to evaluate acute toxicity of an influenza vaccine
title_short Development of a preclinical humanized mouse model to evaluate acute toxicity of an influenza vaccine
title_sort development of a preclinical humanized mouse model to evaluate acute toxicity of an influenza vaccine
topic Research Paper: Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995229/
https://www.ncbi.nlm.nih.gov/pubmed/29899819
http://dx.doi.org/10.18632/oncotarget.25399
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