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

Tamsin Cargill, Paola Cicconi + Show 13 more

Open Access

https://doi.org/10.1016/j.jhepr.2023.100885

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Abstract

Background & AimsMillions 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. MethodsHere 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). ResultsVaccination 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. ConclusionsChAdOx1-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 implicationsTherapeutic 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 RegistrationThis study is registered at ClinicalTrials.gov (NCT04297917).

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