INTERFACE
Research type
Research Study
Full title
INTERFACE: The interplay between HBV infection and the PD-1/PD-L1 pathway of immune modulation
IRAS ID
245799
Contact name
Daniel Neill
Contact email
Sponsor organisation
University of Liverpool
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
This study will investigate the relationship between hepatitis B virus (HBV) replication and the PD-1/PD-L1 pathway of immune modulation that is proposed to play a key role in virus persistence. The overarching scientific aim is to obtain a characterisation of populations showing different forms of HBV expression, and thereby identify how novel biomarkers can inform and guide novel HBV curative strategies. The scientific approach will involve obtaining blood samples from patients with distinct HBV profiles, including subjects with resolved infection, subjects with chronic infection and either low or high levels of virus replication, and subjects carrying different HBV genetic variants. Sample collection will take place both cross-sectionally and prospectively at three sampling points over a period of 24 months. In addition to freshly collected blood samples, the study will take advantage of a rich sample repository available from two previous HBV studies based in Africa, providing a representation of HBV genotypes that are rarely detected in the UK. Freshly collected venous blood samples will undergo immunological characterisation by flow cytometry (phase 1). In addition, blood samples will be stored for batch testing of virological and immunological markers (phase 2). Furthermore, in vitro experiments will be carried out to determine to what degree PD-1 and PD-L1 blockers can restore the ability of patient-derived peripheral blood mononuclear cells (PBMC) to mount HBV-specific immune responses (phase 3). Finally, in a subset of patients who give consent to genetic testing, polymorphisms in genes encoding PD-1/PD-L1, HLA Class I alleles, and cellular polymorphisms associated with expression of HBV proteins will be investigated for their relation to responses to PD-1 and PD-L1 blockade (phase 4).
REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
18/YH/0286
Date of REC Opinion
17 Jul 2018
REC opinion
Favourable Opinion