Abstract
Laboratory mice comprise an expeditious model for preclinical vaccine testing; however, vaccine immunogenicity in these models often inadequately translates to humans. Reconstituting physiologic microbial experience to specific pathogen-free (SPF) mice induces durable immunological changes that better recapitulate human immunity. We examined whether mice with diverse microbial experience better model human responses post vaccination. We co-housed laboratory mice with pet-store mice, which have varied microbial exposures, and then assessed immune responses to influenza vaccines. Human transcriptional responses to influenza vaccination are better recapitulated in co-housed mice. Although SPF and co-housed mice were comparably susceptible to acute influenza infection, vaccine-induced humoral responses were dampened in co-housed mice, resulting in poor control upon challenge. Additionally, protective heterosubtypic T cell immunity was compromised in co-housed mice. Because SPF mice exaggerated humoral and T cell protection upon influenza vaccination, reconstituting microbial experience in laboratory mice through co-housing may better inform preclinical vaccine testing.
Original language | English (US) |
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Pages (from-to) | 1815-1827.e6 |
Journal | Cell Host and Microbe |
Volume | 29 |
Issue number | 12 |
DOIs | |
State | Published - Dec 8 2021 |
Bibliographical note
Publisher Copyright:© 2021 Elsevier Inc.
Keywords
- T cell immunity
- dirty mice
- humoral immunity
- influenza virus
- preclinical models
- vaccine