Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Apr 12;229(4):1077-1087.
doi: 10.1093/infdis/jiad340.

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

Sarah Schmidt  1 , Meron Mengistu  2 , Stephane Daffis  2 , Sarah Ahmadi-Erber  1 , Daniela Deutschmann  1 , Tetiana Grigoriev  2 , Ruth Chu  2 , Cleo Leung  2 , Adrian Tomkinson  2 , Mohammad Nizam Uddin  3 , Safiehkhatoon Moshkani  3 , Michael D Robek  3 , Jason Perry  2 , Henning Lauterbach  1 , Klaus Orlinger  1 , Simon P Fletcher  2 , Scott Balsitis  2
Affiliations

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

Sarah Schmidt et al. J Infect Dis. .

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.

Keywords: arenavirus; hepatitis b; therapeutic vaccine; viral vector.

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest . M. M., S. D., T. G., R. C., C. L., A. T., J. P., S. P. F., and S. B. are or were employees of Gilead Sciences. S. S., S. A. E., D. D., H. L., and K. O. are employees of Hookipa Pharma. M. D. R. has financial relationships with CaroGen Corporation, received royalties from a Yale University patent, and received research funding from Gilead Sciences. Al; other authors reported no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

References

Publication types

Grants and funding