Journal article
Mice with diverse microbial exposure histories as a model for preclinical vaccine testing
Cell host & microbe, Vol.29(12), pp.1815-1827.e6
11/2021
DOI: 10.1016/j.chom.2021.10.001
PMCID: PMC8665115
PMID: 34731647
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.
Keywords: T cell immunity; dirty mice; humoral immunity; influenza virus; preclinical models; vaccine.
Copyright © 2021 Elsevier Inc. All rights reserved.
Details
- Title: Subtitle
- Mice with diverse microbial exposure histories as a model for preclinical vaccine testing
- Creators
- Jessica K Fiege - University of MinnesotaKatharine E Block - University of MinnesotaMark J Pierson - University of MinnesotaHezkiel Nanda - University of MinnesotaFrances K Shepherd - University of MinnesotaClayton K Mickelson - University of MinnesotaJ. Michael Stolley - University of MinnesotaWilliam E Matchett - University of MinnesotaSathi Wijeyesinghe - University of MinnesotaDavid K Meyerholz - University of IowaVaiva Vezys - University of MinnesotaSteven S Shen - University of MinnesotaSara E Hamilton - University of MinnesotaDavid Masopust - University of MinnesotaRyan A Langlois - University of Minnesota
- Resource Type
- Journal article
- Publication Details
- Cell host & microbe, Vol.29(12), pp.1815-1827.e6
- DOI
- 10.1016/j.chom.2021.10.001
- PMID
- 34731647
- PMCID
- PMC8665115
- ISSN
- 1931-3128
- eISSN
- 1934-6069
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: 75N93019C00051, R01 AI116678, R01 AI132962, R01 AI150600, T32 HL007741; DOI: 10.13039/100000016, name: U.S. Department of Health and Human Services, award: HHSN272201400005C; DOI: 10.13039/100000060, name: National Institute of Allergy and Infectious Diseases
- Language
- English
- Date published
- 11/2021
- Academic Unit
- Pathology
- Record Identifier
- 9984201257602771
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