Theoretical modeling of hepatitis C acute infection in liver-humanized mice support pre-clinical assessment of candidate viruses for controlled-human-infection studies
Designing and carrying out a controlled human infection (CHI) model for hepatitis C virus (HCV) is critical for vaccine development. However, key considerations for a CHI model protocol include understanding of the earliest viral-host kinetic events during the acute phase and susceptibility of the viral isolate under consideration for use in the CHI model to antiviral treatment before any infections in human volunteers can take place. Humanized mouse models lack adaptive immune responses but provide a unique opportunity to obtain quantitative understanding of early HCV kinetics and develop mathematical models to further understand viral and innate immune response dynamics during acute HCV infection. We show that the models reproduce the measured HCV kinetics in humanized mice, which are consistent with early acute HCV-host dynamics in immunocompetent chimpanzees. Our findings suggest that humanized mice are well-suited to support development of a CHI model. In-silico and in-vivo modeling estimates provide a starting point to characterize candidate viruses for testing in CHI model studies.
Authors
- Chise Tateno-Mukaidani
- Kazuaki Chayama (ORCID: https://orcid.org/0000-0002-5530-5341)
- Scott J. Cotler (ORCID: https://orcid.org/0000-0003-2564-7786)
- Harel Dahari (ORCID: https://orcid.org/0000-0002-3357-1817)
- Jordan J. Feld (ORCID: https://orcid.org/0000-0003-2640-2211)
- Hiromi Abe‐Chayama (ORCID: https://orcid.org/0000-0002-7665-900X)
- Zhenzhen Shi (ORCID: https://orcid.org/0000-0001-9922-3957)
- Yuji Ishida (ORCID: https://orcid.org/0000-0003-1855-6325)
- Marian Major (ORCID: https://orcid.org/0000-0003-0874-359X)
- Nicholson Collier (ORCID: https://orcid.org/0000-0002-2376-4156)
- Jonathan Ozik (ORCID: https://orcid.org/0000-0002-3495-6735)
- A. Josephson
- A. Mhlanga
Institutions
- Hiroshima University (JP)
- Argonne National Laboratory (US)
- Center for Biologics Evaluation and Research (US)
- University Health Network (CA)
- Loyola University Chicago (US)
- Toronto General Hospital (CA)
- University of Chicago (US)
- PhoenixBio (Japan) (JP)
- Hiroshima Minami High School (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
Publication Details
- Journal
- Scientific Reports
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1038/s41598-024-83104-0
- Citations
- 1
- Primary Topic
- Hepatitis C virus research
- Type
- article
- Field-Weighted Citation Impact
- 0.37
Funders
- Japan Agency for Medical Research and Development
- National Institutes of Health
- Canadian Institutes of Health Research
- Argonne National Laboratory