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Mice with diverse microbial exposure histories as a model for preclinical vaccine testing
Jessica K Fiege1, Katharine E Block2, Mark J Pierson2
1Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
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.
Insights
Introducing diverse microbes to lab mice via co-housing improves preclinical vaccine modeling. This approach better mimics human immune responses to influenza vaccines, enhancing their predictive value for human immunity.
Area of Science:
- Immunology
- Microbiome research
- Vaccinology
Background:
- Laboratory mice are crucial for preclinical vaccine testing.
- Current models often fail to accurately predict human immune responses.
- Specific pathogen-free (SPF) mice lack diverse microbial exposure, limiting their translational relevance.
Purpose of the Study:
- To investigate if diverse microbial exposure in mice enhances the modeling of human immune responses to influenza vaccines.
- To compare the immunogenicity and protective efficacy of influenza vaccines in mice with standard SPF conditions versus those with diverse microbial experience.
Main Methods:
- Co-housing of specific pathogen-free (SPF) laboratory mice with pet-store mice to introduce diverse microbial exposures.
- Assessment of immune responses, including transcriptional profiles, to influenza vaccination.
- Evaluation of vaccine-induced protection against influenza challenge, including humoral and T-cell mediated immunity.
Main Results:
- Co-housed mice better recapitulated human transcriptional responses to influenza vaccination.
- While susceptibility to acute infection was similar, vaccine-induced humoral responses were reduced in co-housed mice.
- Protective heterosubtypic T-cell immunity was compromised in co-housed mice compared to SPF mice.
Conclusions:
- Reconstituting diverse microbial experience in laboratory mice through co-housing may improve preclinical vaccine testing.
- This approach offers a more physiologically relevant model for predicting human vaccine efficacy.
- Further research is needed to optimize microbial reconstitution strategies for enhanced vaccine immunogenicity prediction.
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