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

TitleSelective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses.
Publication TypeJournal Article
Year of Publication2018
AuthorsDouam, F, Ziegler, CGK, Hrebikova, G, Fant, B, Leach, R, Parsons, L, Wang, W, Gaska, JM, Winer, BY, Heller, B, Shalek, AK, Ploss, A
JournalNat Commun
Volume9
Issue1
Pagination5031
Date Published2018 11 28
ISSN2041-1723
KeywordsAnimals, Humans, Killer Cells, Natural, Mice, Myeloid Cells, Transcriptome, Vaccines, Attenuated, Yellow Fever Vaccine, Yellow fever virus
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.

DOI10.1038/s41467-018-07478-2
Alternate JournalNat Commun
PubMed ID30487575
PubMed Central IDPMC6262001
Grant ListRM1 HG006193 / HG / NHGRI NIH HHS / United States