Journal
CELL HOST & MICROBE
Volume 29, Issue 12, Pages 1815-+Publisher
CELL PRESS
DOI: 10.1016/j.chom.2021.10.001
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Funding
- NIH [R01 AI132962, R01 AI150600, R01 AI116678, T32 HL007741]
- NIH CIVIC contract [75N93019C00051]
- NIAID, NIH
- department of Health and Human Services, under CEIRS [HHSN272201400005C]
- UMN Flow Cytometry Resource Facility
- UMN Genomics Center
- CFI Dirty Mouse Colony
- BSL-3 Program
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Laboratory mice co-housed with pet store mice, which have diverse microbial exposures, better mimic human immune responses to influenza vaccines. While both SPF and co-housed mice showed similar susceptibility to acute influenza infection, vaccine-induced humoral and T cell immune responses were dampened in the co-housed mice, leading to poor control upon challenge.
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.
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