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Humanized mice: novel model for studying mechanisms of human immune-based therapies

  • Immunology & Microbiology in Miami
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Abstract

The lack of relevant animal models is the major bottleneck for understanding human immunology and immunopathology. In the last few years, a novel model of humanized mouse has been successfully employed to investigate some of the most critical questions in human immunology. We have set up and tested in our laboratory the latest technology for generating mice with a human immune system by reconstituting newborn immunodeficient NOD/SCID-γ −/−c mice with human fetal liver-derived hematopoietic stem cells. These humanized mice have been deemed most competent as human models in a thorough comparative study with other humanized mouse technologies. Lymphocytes in these mice are of human origin while other hematopoietic cells are chimeric, partly of mouse and partly of human origin. We demonstrate that human CD8 T lymphocytes in humanized mice are fully responsive to our novel cell-based secreted heat shock protein gp96HIV-Ig vaccine. We also show that the gp96HIV-Ig vaccine induces powerful mucosal immune responses in the rectum and the vagina, which are thought to be required for protection from HIV infection. We posit the hypothesis that vaccine approaches tested in humanized mouse models can generate data rapidly, economically and with great flexibility (genetic manipulations are possible), to be subsequently tested in larger nonhuman primate models and humans.

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Acknowledgments

The work is supported by the NIAID R33 AI 073234, NCATS NIH UL1TR000460 and 1KL2TR000461, Miami-CFAR and NIH P30A1073961, Biopsychosocial Research Training In Immunology and AIDS 5T32MH018917-22, National Cancer Institute, Center for Cancer Research and support from the Alliance for Cancer Gene Therapy (ACGT), New York.

Conflict of interest

Dr. E. R. Podack and the University of Miami have financial interest and hold equity in a commercial enterprise developing this vaccine technology.

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  1. Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA

    Louis Gonzalez, Natasa Strbo & Eckhard R. Podack

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  1. Louis Gonzalez
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  2. Natasa Strbo
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  3. Eckhard R. Podack
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Correspondence to Eckhard R. Podack.

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Gonzalez, L., Strbo, N. & Podack, E.R. Humanized mice: novel model for studying mechanisms of human immune-based therapies. Immunol Res 57, 326–334 (2013). https://doi.org/10.1007/s12026-013-8471-2

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