biostudies-literatureFiege JKNational Institute of Allergy and Infectious DiseasesU.S. Department of Health and Human ServicesNIAID NIH HHSNHLBI NIH HHSNational Institutes of Health1815-1827.e6https://www.ebi.ac.uk/biostudies/studies/S-EPMC8665115biostudies-literatureUnknown29(12)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 Cell host & microbeMice with diverse microbial exposure histories as a model for preclinical vaccine testing.PMC866511575N93019C00051R01 AI132962R01 AI116678R01 AI150600R01 AI143828T32 HL007741HHSN272201400005CMickelson CKShepherd FKMatchett WEMeyerholz DKStolley JMNanda HHamilton SEBlock KEFiege JKLanglois RAVezys VWijeyesinghe SPierson MJShen SSMasopust DfalseMice with diverse microbial exposure histories as a model for preclinical vaccine testing.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 2021-01-01T00:00:00Z2021 Dec2026-05-09T22:38:40.96Z2025-02-19T03:26:21.098ZS-EPMC86651153473164710.1016/j.chom.2021.10.001