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

JHEP Reports (Nov 2023)

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

Affiliations

Tamsin Cargill: Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK; Corresponding author. Address: Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, South Parks Road, Oxford OX1 3SY, UK. Tel.: +44 1865 281547.
Paola Cicconi: Jenner Vaccine Trials Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK
Anthony Brown: Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Louise Holland: Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK; Jenner Vaccine Trials Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK
Benaka Karanth: Vaccitech, Harwell, Didcot, UK
Kathryn Rutkowski: Vaccitech, Harwell, Didcot, UK
Emily Ashwin: Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK; Jenner Vaccine Trials Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK
Reena Mehta: Vaccitech, Harwell, Didcot, UK
Senthil Chinnakannan: Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Sarah Sebastian: Vaccitech, Harwell, Didcot, UK
Louise Bussey: Vaccitech, Harwell, Didcot, UK
Henrik Sorensen: Vaccitech, Harwell, Didcot, UK
Paul Klenerman: Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK; Oxford NIHR Biomedical Research Centre, University of Oxford, The Joint Research Office, OUH Cowley, Oxford, UK
Thomas Evans: Vaccitech, Harwell, Didcot, UK
Eleanor Barnes: Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK; Oxford NIHR Biomedical Research Centre, University of Oxford, The Joint Research Office, OUH Cowley, Oxford, UK; Corresponding author. Address: Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, South Parks Road, Oxford OX1 3SY, UK. Tel.: +44 1865 281547.

Journal volume & issue: Vol. 5, no. 11
p. 100885

Abstract

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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).

Published in JHEP Reports

ISSN: 2589-5559 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.journals.elsevier.com/jhep-reports

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