Biological Sciences Division
Published December 30, 2024 | Version v1
Journal article Open

Theoretical modeling of hepatitis C acute infection in liver-humanized mice support pre-clinical assessment of candidate viruses for controlled-human-infection studies

Creators

  • 1. Loyola University Chicago
  • 2. PhoenixBio Co., Ltd.
  • 3. University of Chicago
  • 4. Hiroshima University
  • 5. Food and Drug Administration
  • 6. Toronto General Hospital
  • 7. Hiroshima Institute of Life Sciences

Description

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.

Data availability

We provide all the raw data in Supplementary Table S3.

Files

Theoretical-modeling-of-hepatitis-C-acute-infection-in-liver-humanized-mice-support-pre-clinical-assessment.pdf

Files (2.8 MB)

Additional details

Identifiers

DOI
10.1038/s41598-024-83104-0
Other
oai:uchicago.tind.io:14335

Funding

National Institutes of Health
R01GM121600
National Institutes of Health
R01AI078881
National Institutes of Health
R01AI158666
Japan AMED
JP23fk0310513
Canadian Institutes of Health Research
AFF funding

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Public Health Sciences