Challenge Inoculum for Hepatitis C Virus Controlled Human Infection Model

T Jake Liang; John L M Law; Thomas Pietschmann; Stuart C Ray; Jens Bukh; Rowena Bull; Raymond T Chung; D Lorne Tyrrell; Michael Houghton; Charles M Rice

doi:10.1093/cid/ciad336

Challenge Inoculum for Hepatitis C Virus Controlled Human Infection Model

Clin Infect Dis. 2023 Aug 14;77(Suppl 3):S257-S261. doi: 10.1093/cid/ciad336.

Authors

Affiliations

¹ Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
² Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
³ Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
⁴ Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁵ Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital; Hvidovre and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁶ Liver Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁷ School of Biomedical Sciences and The Kirby Institute, Medicine and Health, University of New South Wales, Sydney, Australia.
⁸ Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, USA.

Abstract

For any controlled human infection model (CHIM), a safe, standardized, and biologically relevant challenge inoculum is necessary. For hepatitis C virus (HCV) CHIM, we propose that human-derived high-titer inocula of several viral genotypes with extensive virologic, serologic, and molecular characterizations should be the most appropriate approach. These inocula should first be tested in human volunteers in a step-wise manner to ensure safety, reproducibility, and curability prior to using them for testing the efficacy of candidate vaccines.

Keywords: acute hepatitis; risk-benefit analysis; treatment; vaccine development.

Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Hepacivirus* / genetics
Hepatitis C*
Humans
Reproducibility of Results