Optimizing mouse models for mRNA vaccines: addressing dose translation challenges
Abstract
Abstract 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.
Article Details
Authors (50)
Zi Wei Chang
Yong Jie Tan
Yiyu Liao
Yun Shan Goh
Syed Ridwan Kabir
Yuqian Wang
Pei Xiang Hor
Chiew Yee Loh
Yuling Huang
Bei Wang
State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research and Shuguang Hospital
Siti Nazihah Mohd Salleh
Eve Zi Xian Ngoh
Angeline Rouers
Anthony Torres-Ruesta
Nathan Wong
Alice Soh Meoy Ong
Adeline Chiew Yen Chua
Samantha Nguee
Vanessa Neo
Isaac Kai Jie Kam
Ajayanandan Yadunandan
Sooriya Kannan Selvam
Jarvis Goh
Ng Kah Ying
Sim Xin Yi
Wong Wei Lun
Anna Xinyi Loo
Liang Hui Loo
Jocelyn Jin Yu
Zheng Kuang Soh
Yi Qing Chin
Jonathan Jordon Lim
Juwinda Ongko
Eshele Anak Libau
Celine Theo
Mohammed Ridzwan Bin Abdullah
Shiau Hui Diong
He Ping Yeo
Surinder Pada
Louisa Jin Sun
Desmond Luan Seng Ong
Jyoti Somani
Eng Sing Lee
Cheng-I Wang
David C. Lye
Barnaby E. Young
Matthew Zirui Tay
Lisa F. P. Ng
Keisuke Ejima
Lee Kong Chian School of Medicine, Nanyang Technological University
Laurent Renia