Optimizing mouse models for mRNA vaccines: addressing dose translation challenges

The development of mRNA vaccines has significantly advanced global health during the COVID-19 pandemic. However, translating effective vaccine doses from preclinical animal models to human clinical use remains poorly understood. In this study, we evaluated antibody responses and repertoire diversity across different BNT162b2 mRNA vaccine doses in mice, while comparing the results with human data through mathematical modeling. We observed that 1 μg BNT162b2 dose regimen induced a persistent antibody response and broad antibody repertoire for up to 16 weeks in mice. Conversely, 0.05 μg BNT162b2 dose regimen resulted in waning antibody responses and narrowed antibody repertoires over the same period, resembling responses observed in humans vaccinated with 30 μg BNT162b2 dose regimen. An empirical dose translation approach revealed a discrepancy in dose relevance between the 1 μg commonly used in the in vivo mice model and the 30 μg used for vaccination in human. Therefore, it is crucial to re-evaluate the appropriate mRNA vaccine dose for in vivo mice models to accurately reflect human responses.