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Updated: Mar 28, 2026
Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
Dirty mice better recapitulate key features of mRNA vaccine immunogenicity observed in humans
Beatriz Praena1,2, Frances K Shepherd1,2, Cera A McDonald1,2
1Department of Microbiology and Immunology, University of Minnesota, Minneapolis MN, USA.
Abstract:
Although specific pathogen free (SPF) mice have traditionally been used to test candidate vaccines, recent work has demonstrated that "dirty" mice with broad microbial exposure more appropriately recapitulate human immune responses. Using a model where lab mice are co-housed with pet store mice, we modeled SARS-CoV-2 mRNA vaccine responses in dirty and traditional SPF models. We found that dirty mice show reduced serum spike-binding antibody titers after prime and require a second booster dose to reach SPF-level spike antibody titers. Additionally, spike antibodies showed faster waning in dirty mice through 5 months post-vaccination, and neutralizing activity of these antibodies were reduced against Omicron variants, directly comparable with observations in humans. We further investigated the seasonality and consistency of pathogens in cohoused mice, and the impact of serial microbial exposure on our animal model system. We found that pathogen exposure and T cell activation remained consistent over time, and that a single co-housing event was sufficient to provide broad microbial exposure. This work demonstrates that the dirty mouse co-housing system is a promising, translationally representative approach to screen candidate mRNA vaccines for efficacy and durability prior to human clinical trials.
Insights
Mice with microbial exposure ("dirty" mice) showed reduced SARS-CoV-2 mRNA vaccine antibody responses and faster waning compared to traditional SPF mice. This dirty mouse model better reflects human immune responses to vaccines.
Area of Science:
- Immunology
- Vaccinology
- Microbiome Research
Background:
- Specific pathogen-free (SPF) mice are traditional models for vaccine testing.
- Recent studies suggest "dirty" mice with broad microbial exposure better mimic human immune responses.
- SARS-CoV-2 mRNA vaccines require boosters and show waning efficacy over time in humans.
Purpose of the Study:
- To model SARS-CoV-2 mRNA vaccine responses in "dirty" versus SPF mice.
- To assess the impact of microbial exposure on vaccine efficacy and antibody durability.
- To evaluate the utility of the dirty mouse model for preclinical vaccine screening.
Main Methods:
- Co-housing of lab mice with pet store mice to create a "dirty" mouse model.
- Administration of SARS-CoV-2 mRNA vaccine (prime and boost).
- Measurement of serum spike-binding antibody titers and neutralizing activity.
- Assessment of antibody waning over 5 months post-vaccination.
- Investigation of pathogen consistency and T cell activation in co-housed mice.
Main Results:
- Dirty mice exhibited reduced serum spike-binding antibody titers after initial vaccination.
- A booster dose was required for dirty mice to achieve SPF-level antibody titers.
- Spike antibodies showed faster waning in dirty mice compared to SPF mice.
- Neutralizing activity against Omicron variants was reduced in dirty mice's antibodies.
- Pathogen exposure and T cell activation remained consistent over time in co-housed mice.
Conclusions:
- The dirty mouse model provides a more translationally relevant system for preclinical mRNA vaccine evaluation.
- This model accurately recapitulates human observations of reduced vaccine efficacy and faster waning.
- The dirty mouse co-housing system is a promising approach for screening vaccine efficacy and durability before human trials.
