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Optimizing mouse models for mRNA vaccines: addressing dose translation challenges.

Zi Wei Chang1, Yong Jie Tan1, Yiyu Liao2

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Evaluating messenger RNA (mRNA) vaccine doses in mice requires re-evaluation. Lower mouse doses may not accurately predict human immune responses to mRNA vaccines like BNT162b2.

Keywords:
AntibodiesBNT162b2Dose translationHumanMousemRNA vaccine

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Area of Science:

  • Immunology
  • Vaccinology
  • Pharmacology

Background:

  • Messenger RNA (mRNA) vaccines, such as BNT162b2, have been crucial for global health.
  • Translating effective preclinical vaccine doses to human clinical use is challenging and not well understood.

Purpose of the Study:

  • To evaluate antibody responses and repertoire diversity across different BNT162b2 mRNA vaccine doses in mice.
  • To compare mouse data with human data using mathematical modeling to understand dose translation.

Main Methods:

  • Administered varying doses of BNT162b2 mRNA vaccine (1 μg and 0.05 μg) to mice.
  • Monitored antibody responses and repertoire diversity for 16 weeks.
  • Utilized mathematical modeling to compare mouse and human vaccination data.

Main Results:

  • A 1 μg BNT162b2 dose in mice induced persistent antibodies and broad repertoire for 16 weeks.
  • A 0.05 μg BNT162b2 dose in mice showed waning antibodies and narrowed repertoire, similar to human 30 μg dose responses.
  • Empirical dose translation revealed a significant discrepancy between mouse (1 μg) and human (30 μg) BNT162b2 vaccine doses.

Conclusions:

  • The standard 1 μg mouse dose for BNT162b2 mRNA vaccines may not accurately reflect human immune responses.
  • Re-evaluating mRNA vaccine doses in preclinical mouse models is critical for better prediction of human outcomes.
  • Accurate dose translation is essential for developing effective mRNA vaccines for human use.