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, Sarah Schmidt Hookipa Pharma , New York, New York , USA Search for other works by this author on: Oxford Academic Meron Mengistu Gilead Sciences , Foster City, California , USA Search for other works by this author on: Oxford Academic Stephane Daffis Gilead Sciences , Foster City, California , USA Search for other works by this author on: Oxford Academic Sarah Ahmadi-Erber Hookipa Pharma , New York, New York , USA Search for other works by this author on: Oxford Academic Daniela Deutschmann Hookipa Pharma , New York, New York , USA Search for other works by this author on: Oxford Academic Tetiana Grigoriev Gilead Sciences , Foster City, California , USA Search for other works by this author on: Oxford Academic Ruth Chu Gilead Sciences , Foster City, California , USA Search for other works by this author on: Oxford Academic Cleo Leung Gilead Sciences , Foster City, California , USA Search for other works by this author on: Oxford Academic Adrian Tomkinson Gilead Sciences , Foster City, California , USA Search for other works by this author on: Oxford Academic Mohammad Nizam Uddin Department of Immunology and Microbial Disease, Albany Medical College , Albany, New York , USA Search for other works by this author on: Oxford Academic
, Safiehkhatoon Moshkani Department of Immunology and Microbial Disease, Albany Medical College , Albany, New York , USA Search for other works by this author on: Oxford Academic Michael D Robek Department of Immunology and Microbial Disease, Albany Medical College , Albany, New York , USA Search for other works by this author on: Oxford Academic Jason Perry Gilead Sciences , Foster City, California , USA Search for other works by this author on: Oxford Academic Henning Lauterbach Hookipa Pharma , New York, New York , USA Search for other works by this author on: Oxford Academic Klaus Orlinger Hookipa Pharma , New York, New York , USA Search for other works by this author on: Oxford Academic Simon P Fletcher Gilead Sciences , Foster City, California , USA Search for other works by this author on: Oxford Academic Scott Balsitis Gilead Sciences , Foster City, California , USA Correspondence: Scott Balsitis, PhD, Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404 (scott.balsitis@gilead.com). Search for other works by this author on: Oxford Academic
The Journal of Infectious Diseases, Volume 229, Issue 4, 15 April 2024, Pages 1077–1087, https://doi.org/10.1093/infdis/jiad340
Published:
21 August 2023
Article history
Received:
18 April 2023
Editorial decision:
07 August 2023
Accepted:
17 August 2023
Published:
21 August 2023
Corrected and typeset:
19 September 2023
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Sarah Schmidt, Meron Mengistu, Stephane Daffis, Sarah Ahmadi-Erber, Daniela Deutschmann, Tetiana Grigoriev, Ruth Chu, Cleo Leung, Adrian Tomkinson, Mohammad Nizam Uddin, Safiehkhatoon Moshkani, Michael D Robek, Jason Perry, Henning Lauterbach, Klaus Orlinger, Simon P Fletcher, Scott Balsitis, Alternating Arenavirus Vector Immunization Generates Robust Polyfunctional Genotype Cross-Reactive Hepatitis B Virus–Specific CD8 T-Cell Responses and High Anti–Hepatitis B Surface Antigen Titers, The Journal of Infectious Diseases, Volume 229, Issue 4, 15 April 2024, Pages 1077–1087, https://doi.org/10.1093/infdis/jiad340
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Abstract
Hepatitis B Virus (HBV) is a major driver of infectious disease mortality. Curative therapies are needed and ideally should induce CD8 T cell-mediated clearance of infected hepatocytes plus anti-hepatitis B surface antigen (HBsAg) antibodies (anti-HBs) to neutralize residual virus. We developed a novel therapeutic vaccine using non-replicating arenavirus vectors. Antigens were screened for genotype conservation and magnitude and genotype reactivity of T cell response, then cloned into Pichinde virus (PICV) vectors (recombinant PICV, GS-2829) and lymphocytic choriomeningitis virus (LCMV) vectors (replication-incompetent, GS-6779). Alternating immunizations with GS-2829 and GS-6779 induced high-magnitude HBV T cell responses, and high anti-HBs titers. Dose schedule optimization in macaques achieved strong polyfunctional CD8 T cell responses against core, HBsAg, and polymerase and high titer anti-HBs. In AAV-HBV mice, GS-2829 and GS-6779 were efficacious in animals with low pre-treatment serum HBsAg. Based on these results, GS-2829 and GS-6779 could become a central component of cure regimens.
arenavirus, hepatitis b, therapeutic vaccine, viral vector
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/pages/standard-publication-reuse-rights)
Topic:
- antigens
- cross reactions
- genotype
- hepatitis b surface antigens
- hepatocytes
- immunization
- lymphocytic choriomeningitis virus
- macaca
- t-lymphocytes
- vaccines
- hepatitis b virus
- mice
- arenaviruses
Issue Section:
Major Article > Viruses
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