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A Lung-Immune Dual-Humanized Mouse Using Cryopreserved Tissue Enables Infection and Immune Profiling of Human Common
Chunyu Cheng1, Jing Sun2,3, Chun Lu1
1MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210093, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|December 7, 2025
Summary
A new model using cryopreserved human lung tissue enables robust infection by common cold coronaviruses (CCCoVs). This breakthrough aids research into CCCoV evolution, immune responses, and potential pan-coronavirus vaccines.
Area of Science:
- Virology
- Immunology
- Respiratory Medicine
Background:
- Human common cold coronaviruses (CCCoVs) are significant for understanding viral evolution and immunity.
- Existing animal models are limited by human-specific tropism and co-infections, hindering pathogenesis studies.
- Previous models relied on fresh human tissues, posing logistical challenges.
Purpose of the Study:
- To develop and validate a scalable animal model for studying CCCoVs.
- To investigate CCCoV tropism, pathogenesis, and immune interactions in a humanized environment.
- To assess therapeutic interventions and cross-protective immune responses.
Main Methods:
- Optimized a transplantation strategy using cryopreserved human fetal lung tissue in mice.
- Validated the model's susceptibility to all four major CCCoVs (229E, NL63, OC43, HKU1).
- Assessed therapeutic efficacy (Paxlovid) and analyzed human immune cell phenotypes and T cell responses.
Main Results:
- Achieved enhanced engraftment efficiency with cryopreserved lung tissue.
- Demonstrated robust infection by all four major CCCoVs.
- Showcased therapeutic efficacy of Paxlovid against HKU1 and revealed distinct immune cell phenotypes.
- Enabled validation of virus-specific T cell responses and SARS-CoV-2 cross-reactivity.
Conclusions:
- Established a scalable, cryopreserved-tissue-based platform for respiratory virus research.
- Overcame limitations of human-specific tropism and complex co-infections.
- Provides a valuable tool for dissecting immune-pathogen interactions and developing novel therapeutics and vaccines.
