Original ResearchClinical—LiverA Poxvirus Vaccine Is Safe, Induces T-Cell Responses, and Decreases Viral Load in Patients With Chronic Hepatitis C
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Study Design
The study was conducted in full accordance with the 1996 Declaration of Helsinski and Good Clinical Practice with approval from the ethical review committee (Comité de Protection des Personnes) of Lyon (France). All patients provided written informed consent before participating in any study-related activity (The trial is referenced in ClinicalTrials.gov; under the identifier: NCT00529321).
This study was a multicenter, open-label, dose escalation study. TG4040 was administered subcutaneously at
Results
A total of 15 patients was enrolled in the study. The first 9 patients were sequentially treated in 3 cohorts (Figure 1). Each cohort consisted of 3 patients receiving 3 subcutaneous injections of TG4040 on days 1, 8, and 15 at a dose of either 106, 107, or 108 PFU depending on their inclusion in cohort 1, 2, or 3 respectively. All patients were followed up to at least 6 months after the first injection. Patients treated at the 108 PFU dose received a TG4040 boost injection at the same dose, 6
Discussion
In this study, we report for the first time the clinical evaluation of a vector-based T-cell inducing vaccine for the treatment of CHC. The primary end point of the study was reached because TG4040 was shown to be safe at all doses tested. We did not observe any significant flares of hepatitis. Specifically, the only related TG4040 increase seen was transient and remained below 4 times the upper limit of the normal. Most of the reported AEs were typical of poxvirus-based vaccination, ie,
Acknowledgments
The authors thank Dr C. Brandt and Professor P. Bousquet from the Centre d'Investigation Clinique-Inserm 2, University Hospital Strasbourg, for their assistance in the conduct of this study; Professor Nicolas Meyer from the service de Santé Publique, University Hospital Strasbourg, for helpful discussions; B. Marie Bastien, C. Zemmour, and C. Ezzode for statistical input; and T. Nguyen for technical advice.
The corresponding authors had full access to all of the data and take full responsibility
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2019, Infection, Genetics and EvolutionCitation Excerpt :The findings correspondingly disclosed that in 33% of cases (5 out of 15 patients with CHC), immune cellular immunity was achieved 6 months after the first dose of the vaccine. Also, in 8 patients, the level of RNA of the HCV virus significantly decreased (Habersetzer et al., 2011). In a further clinical trial, Swadling et al., 2014 used adenoviruses of monkies to vaccinate the patients.
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2017, Plotkin's VaccinesLarge scale production of a mammalian cell derived quadrivalent hepatitis C virus like particle vaccine
2016, Journal of Virological MethodsCitation Excerpt :Numerous HCV vaccine candidates have been reported, including recombinant E1 and E2 proteins (Colombatto et al., 2014; Houghton, 2011), synthetic peptides (Chua et al., 2008; Torresi et al., 2007a,b), DNA (Grubor-Bauk et al., 2016; Gummow et al., 2015; Puig et al., 2006; Sallberg et al., 2009a), recombinant adenoviral and prime-boost strategies with MVA vaccines or recombinant E1E2 glycoproteins (Chmielewska et al., 2014; Folgori et al., 2006; Thammanichanond et al., 2008). However, few have progressed to Phase I and II clinical trials in humans including synthetic peptide-based vaccines (Klade et al., 2012), recombinant poxvirus (Habersetzer et al., 2011), adenoviral and MVA vaccines (Barnes et al., 2012; Swadling et al., 2014), and DNA vaccines (Castellanos et al., 2010; Sallberg et al., 2009b). These vaccines have resulted in the production of robust cross reactive HCV-specific CD4+ and CD8+ T cell responses and reductions in HCV viral load.
Conflicts of interest These authors disclose the following: Christine Bain, Jean-Yves Bonnefoy, Geneviève Inchauspé, Géraldine Honnet, Delphine Agathon, Martin Baudin, Jean-Marc Limacher, and Myew-Ling Toh are employees of Transgene. The remaining authors disclose no conflicts.
Funding Supported by Transgene, Strasbourg, France, and Biotherapic Grant from French Ministry of Research and Industry sponsored by Lyon Biopôle, France.