HBV001: Phase I study evaluating the safety and immunogenicity of the therapeutic vaccine ChAdOx1-HBV

Tamsin Cargill; Paola Cicconi; Anthony Brown; Louise Holland; Benaka Karanth; Kathryn Rutkowski; Emily Ashwin; Reena Mehta; Senthil Chinnakannan; Sarah Sebastian; Louise Bussey; Henrik Sorensen; Paul Klenerman; Thomas Evans; Eleanor Barnes

doi:10.1016/j.jhepr.2023.100885

HBV001: Phase I study evaluating the safety and immunogenicity of the therapeutic vaccine ChAdOx1-HBV

JHEP Rep. 2023 Aug 18;5(11):100885. doi: 10.1016/j.jhepr.2023.100885. eCollection 2023 Nov.

Authors

Tamsin Cargill^{1

2}, Paola Cicconi³, Anthony Brown¹, Louise Holland^{2

3}, Benaka Karanth⁴, Kathryn Rutkowski⁴, Emily Ashwin^{2

3}, Reena Mehta⁴, Senthil Chinnakannan¹, Sarah Sebastian⁴, Louise Bussey⁴, Henrik Sorensen⁴, Paul Klenerman^{1

2

5}, Thomas Evans⁴, Eleanor Barnes^{1

2

5}

Affiliations

¹ Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
² Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
³ Jenner Vaccine Trials Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK.
⁴ Vaccitech, Harwell, Didcot, UK.
⁵ Oxford NIHR Biomedical Research Centre, University of Oxford, The Joint Research Office, OUH Cowley, Oxford, UK.

Abstract

Background & aims: Millions of people worldwide are infected chronically with HBV, which results in significant morbidity and mortality. Therapeutic vaccination is a strategy that aims to induce functional cure by restoring cellular immunity to HBV. Previously we have shown the candidate HBV immunotherapeutic vaccine ChAdOx1-HBV, encoding all major HBV antigens and a genetic adjuvant (shark invariant chain), is highly immunogenic in mice.

Methods: Here we report the results of HBV001, a first-in-human, phase I, non-randomised, dose-escalation trial of ChAdOx1-HBV assessed in healthy volunteers and patients with chronic HBV (CHB).

Results: Vaccination with a single dose of ChAdOx1-HBV was safe and well tolerated in both healthy and CHB cohorts. Vaccination induced high magnitude HBV-specific T cell responses against all major HBV antigens (core, polymerase, and surface) in healthy volunteers. Responses were detected but lower in patients with CHB. T cells generated by vaccination were cross-reactive between HBV C and D genotypes.

Conclusions: ChAdOx1-HBV is safe and immunogenic in healthy volunteers and patients with CHB. In further studies, ChAdOx1-HBV will be used in combination with other therapeutic strategies with an aim to overcome the attenuated immunogenicity in patients with CHB.

Impact and implications: Therapeutic vaccine ChAdOx1-HBV, a novel treatment for chronic hepatitis B infection (CHB), has been shown to be immunogenic in preclinical studies. In HBV001, a first-in-human phase I study, we show vaccination with ChAdOx1-HBV is safe and generates high magnitude T cell responses in healthy volunteers and lower levels of responses in patients with CHB. This is an important first step in the development of ChAdOx1-HBV as part of a wider therapeutic strategy to induce hepatitis B functional cure, and is of great interest to patients CHB and clinicians treating the condition.

Clinical trials registration: This study is registered at ClinicalTrials.gov (NCT04297917).

Keywords: Chimpanzee adenovirus; Hepatitis B; Shark invariant chain; Vaccine.

Associated data

ClinicalTrials.gov/NCT04297917