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Abstract Details
Immunological Biomarker Discovery in Cure Regimens for Chronic Hepatitis B Virus Infection
J Hepatol. 2022 Mar 5;S0168-8278(22)00127-1. doi: 10.1016/j.jhep.2022.02.020.Online ahead of print.
Adam J Gehring1, Patricia Mendez2, Kirsten Richter3, Hildegund Ertl4, Eric F Donaldson5, Poonam Mishra5, Mala Maini6, Andre Boonstra7, Georg Lauer8, An de Creus9, Kathleen Whitaker10, Sara Ferrando Martinez11, Jessica Weber12, Emily Gainor12, Veronica Miller12
Author information
Toronto Centre for Liver Disease, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Department of Immunology, University of Toronto, Toronto, Ontario, Canada. Electronic address: adam.gehring@uhnresearch.ca.
Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404.
F. Hoffmann-La Roche, Roche Innovation Center Basel, Grenzacher Strasse 124, CH-4070 Basel, Switzerland.
The Wistar Institute, Philadelphia, PA 19104, USA.
Division of Antivirals, Center for Drug Evaluation and Research, US Food and Drug Administration.
Division of Infection and Immunity, University College London, London, UK.
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Janssen Pharmaceuticals, Beerse, Belgium.
Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health, US Food and Drug Administration.
Microbial Sciences, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, US; NeoImmuneTech, LLC 2400 Research Blvd, Suite 250 Rockville, MD 20850.
Forum for Collaborative Research, University of California, Berkeley.
Abstract
There have been unprecedented advances in identifying new targets for chronic hepatitis B therapy to achieve functional cure in patients who would otherwise face lifelong nucleoside analogue treatment. Many of the new investigational therapies either directly target the immune system or are anticipated to impact immunity indirectly through modulation of the viral lifecycle and antigen production. While new viral biomarkers (HBV RNA, HBcAg, small, middle, large HBs isoforms) are proceeding through validation steps in clinical studies, immunological biomarkers are non-existent outside of clinical assays for antibodies to HBs, and HBe. To develop clinically applicable immunological biomarkers to measure mechanisms of action, inform logical combination strategies, and guide clinical management for use and discontinuation of immune-targeting drugs, immune assays must be incorporated into Phase I/II clinical trials. This paper will discuss the importance of sample collection, the assays available for immunological analyses, their advantages/disadvantages and suggestions for their implementation in clinical trials. Careful consideration must be given to ensure appropriate immunological studies are included as a primary component of the trial with deeper immunological analysis provided by ancillary studies. Standardizing immunological assays and data obtained from clinical trials will identify biomarkers that can be deployed in the clinic, independent of specialized immunology laboratories.