Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses

Florian Douam; Carly G K Ziegler; Gabriela Hrebikova; Bruno Fant; Robert Leach; Lance Parsons; Wei Wang; Jenna M Gaska; Benjamin Y Winer; Brigitte Heller; Alex K Shalek; Alexander Ploss

doi:10.1038/s41467-018-07478-2

Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses

Nat Commun. 2018 Nov 28;9(1):5031. doi: 10.1038/s41467-018-07478-2.

Authors

Florian Douam¹, Carly G K Ziegler^{2

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8}, Gabriela Hrebikova¹, Bruno Fant⁹, Robert Leach¹⁰, Lance Parsons¹⁰, Wei Wang¹⁰, Jenna M Gaska¹, Benjamin Y Winer¹, Brigitte Heller¹, Alex K Shalek^{2

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8}, Alexander Ploss¹¹

Affiliations

¹ Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Washington Road, Princeton, NJ, 08544, USA.
² Institute for Medical Engineering & Science (IMES), MIT, Cambridge, MA, 02139, USA.
³ Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02142, USA.
⁴ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
⁵ Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
⁶ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02142, USA.
⁷ Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA, 02139, USA.
⁸ Graduate Program in Biophysics, Harvard Medical School, Boston, MA, 02139, USA.
⁹ Department of Psychiatry, Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
¹⁰ Lewis Sigler Institute for Integrative Genomics, Genomics Core, Carl Icahn Laboratory, Princeton University, Princeton, NJ, 19104, USA.
¹¹ Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Washington Road, Princeton, NJ, 08544, USA. aploss@princeton.edu.

Abstract

Mice engrafted with components of a human immune system have become widely-used models for studying aspects of human immunity and disease. However, a defined methodology to objectively measure and compare the quality of the human immune response in different models is lacking. Here, by taking advantage of the highly immunogenic live-attenuated yellow fever virus vaccine YFV-17D, we provide an in-depth comparison of immune responses in human vaccinees, conventional humanized mice, and second generation humanized mice. We demonstrate that selective expansion of human myeloid and natural killer cells promotes transcriptomic responses akin to those of human vaccinees. These enhanced transcriptomic profiles correlate with the development of an antigen-specific cellular and humoral response to YFV-17D. Altogether, our approach provides a robust scoring of the quality of the human immune response in humanized mice and highlights a rational path towards developing better pre-clinical models for studying the human immune response and disease.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Humans
Killer Cells, Natural / immunology
Killer Cells, Natural / metabolism*
Mice
Myeloid Cells / immunology
Myeloid Cells / metabolism*
Transcriptome / genetics
Vaccines, Attenuated / immunology*
Yellow Fever Vaccine / genetics
Yellow Fever Vaccine / immunology*
Yellow fever virus / genetics
Yellow fever virus / immunology*

Substances

Vaccines, Attenuated
Yellow Fever Vaccine

Abstract

Publication types

MeSH terms

Substances

Grants and funding