Mice with diverse microbial exposure histories as a model for preclinical vaccine testing

Jessica K Fiege; Katharine E Block; Mark J Pierson; Hezkiel Nanda; Frances K Shepherd; Clayton K Mickelson; J. Michael Stolley; William E Matchett; Sathi Wijeyesinghe; David K Meyerholz; Vaiva Vezys; Steven S Shen; Sara E Hamilton; David Masopust; Ryan A Langlois

doi:10.1016/j.chom.2021.10.001

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Mice with diverse microbial exposure histories as a model for preclinical vaccine testing

Journal article

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Mice with diverse microbial exposure histories as a model for preclinical vaccine testing

Jessica K Fiege, Katharine E Block, Mark J Pierson, Hezkiel Nanda, Frances K Shepherd, Clayton K Mickelson, J. Michael Stolley, William E Matchett, Sathi Wijeyesinghe, David K Meyerholz, …

Cell host & microbe, Vol.29(12), pp.1815-1827.e6

11/2021

DOI: 10.1016/j.chom.2021.10.001

PMCID: PMC8665115

PMID: 34731647

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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 Minnesota
Katharine E Block - University of Minnesota
Mark J Pierson - University of Minnesota
Hezkiel Nanda - University of Minnesota
Frances K Shepherd - University of Minnesota
Clayton K Mickelson - University of Minnesota
J. Michael Stolley - University of Minnesota
William E Matchett - University of Minnesota
Sathi Wijeyesinghe - University of Minnesota
David K Meyerholz - University of Iowa
Vaiva Vezys - University of Minnesota
Steven S Shen - University of Minnesota
Sara E Hamilton - University of Minnesota
David Masopust - University of Minnesota
Ryan 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
NLM abbreviation: Cell Host Microbe
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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