한빛사논문
- 조회243
Tak W.Y. 1, Chuang W.-L. 2, Chen C.-Y. 3, Tseng K.-C. 4, Lim Y.-S. 5, Lo G.-H. 6, Heo J. 7, Agarwal K. 8, Bussey L. 9, Teo S.L. 10, Tria A. 10, Brown A. 11, Anderson K. 9, Vardeu A. 9, O’Brien S. 9, Kopycinski J. 9, Rutkowski K. 9, Kolenovska R. 9, Barnes E. 11,12, Evans T.G. 9
1School of Medicine, Kyungpook National University, Kyungpook National University Hospital
2Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
3Chia-Yi Christian Hospital, Chiayi City, Taiwan
4Dalin Tzu Chi General Hospital, Hualien, Taiwan
5Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
6E-Da Hospital, Kaohsiung, Taiwan
7Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
8Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London UK
9Vaccitech, Harwell, UK
10ICON, Singapore
11Nuffield Department of Medicine, Oxford University, Oxford, UK
12Oxford NIHR Biomedical Research Centre, Oxford Hospitals NHS Trust, Oxford, UK
Corresponding author: Evans T.G.
Abstract
Background and aim: The induction of effective CD8+ T cells is thought to play a critical role in the functional cure of chronic hepatitis B (CHB). Additionally, the use of checkpoint inhibitors is being evaluated to overcome T cell dysfunction during CHB.
Approach and results: A chimpanzee adenoviral vector (ChAdOx1-HBV) and a Modified vaccinia Ankara boost (MVA-HBV) encoding the inactivated polymerase, core, and S region from a consensus genotype C HBV were studied. The trial enrolled 55 patients with virally-suppressed CHB virus infection and HBsAg <4,000 IU/mL Group 1 received MVA-HBV intramuscularly (IM) on Day 0 and 28, Group 2 received ChAdOx1-HBV on Day 0/MVA-HBV on Day 28 (VTP-300), Group 3 received VTP-300 + low-dose nivolumab (LDN) on Day 28, and Group 4 received VTP-300 plus LDN with both injections. VTP-300 alone and in combination with LDN was well tolerated with no treatment-related serious adverse events. Reductions of HBsAg were demonstrated in the VTP-300 group 2: 3 of 18 patients with starting HBsAg < 50 IU/ml had durable log10 declines > 0.7 log10 2 months post last-dose. Group 3 (N=18) had reductions in HBsAg of 0.76 log10 and 0.80 log10 3 (p<0.001) at 2 and 7 months post last dose. Two developed persistent non-detectable HBsAg levels. CD4+ and CD8+ antigen-specific T cell responses were generated and there was a correlation between IFN-y ELISpot response and HBsAg decline in Group 2.
Conclusions: VTP-300 induced CD4+ and CD8+ T cells and lowered HBsAg in a subset of patients with baseline values below 100 IU/ml. The addition of LDN resulted in significant reduction in surface antigen. VTP-300 is a promising immunotherapeutic to move forward alone or in combination therapies.
논문정보
- Research article
- 2024년 07월 (BRIC 등록일 2024-07-11)
- 국내+국외 연구진
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