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 and Alexander Ploss ()
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Florian Douam: Princeton University
Carly G. K. Ziegler: MIT
Gabriela Hrebikova: Princeton University
Bruno Fant: Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania
Robert Leach: Genomics Core, Carl Icahn Laboratory, Princeton University
Lance Parsons: Genomics Core, Carl Icahn Laboratory, Princeton University
Wei Wang: Genomics Core, Carl Icahn Laboratory, Princeton University
Jenna M. Gaska: Princeton University
Benjamin Y. Winer: Princeton University
Brigitte Heller: Princeton University
Alex K. Shalek: MIT
Alexander Ploss: Princeton University

Nature Communications, 2018, vol. 9, issue 1, 1-19

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07478-2

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