A meta-analysis of the antiviral activity of the HBV-specific immunotherapeutic TG1050 confirms its value over a wide range of HBsAg levels in a persistent HBV pre-clinical model
| العنوان: | A meta-analysis of the antiviral activity of the HBV-specific immunotherapeutic TG1050 confirms its value over a wide range of HBsAg levels in a persistent HBV pre-clinical model |
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| المؤلفون: | Nathalie Silvestre, Perrine Martin, A. Evlachev, Geneviève Inchauspé, Karine Lélu, Roland Kratzer, Doris Schmitt, Benoit Sansas |
| المصدر: | Human Vaccines & Immunotherapeutics |
| بيانات النشر: | Taylor & Francis, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, HBsAg, Immunology, Short Report, Drug Evaluation, Preclinical, Viremia, immunotherapeutic, medicine.disease_cause, Antiviral Agents, Virus, 03 medical and health sciences, 0302 clinical medicine, Hepatitis B, Chronic, medicine, Immunology and Allergy, Animals, Immunologic Factors, Treatment effect, chronic hepatitis B, TG1050, Pharmacology, Hepatitis B virus, AAV-HBV mouse model, Hepatitis B Surface Antigens, business.industry, Hazard ratio, virus diseases, Viral Load, medicine.disease, digestive system diseases, meta-analysis, Mice, Inbred C57BL, Chronic infection, Disease Models, Animal, 030104 developmental biology, Treatment Outcome, Meta-analysis, DNA, Viral, 030211 gastroenterology & hepatology, Female, business |
| الوصف: | Pre-clinical models mimicking persistent hepatitis B virus (HBV) expression are seldom, do not capture all features of a human chronic infection and due to their complexity, are subject to variability. We report a meta-analysis of seven experiments performed with TG1050, an HBV-targeted immunotherapeutic,1 in an HBV-persistent mouse model based on the transduction of mice by an adeno-associated virus coding for an infectious HBV genome (AAV-HBV). To mimic the clinical diversity seen in HBV chronically infected patients, AAV-HBV transduced mice displaying variable HBsAg levels were treated with TG1050. Overall mean percentages of responder mice, displaying decrease in important clinical parameters i.e. HBV-DNA (viremia) and HBsAg levels, were 52% and 51% in TG1050 treated mice, compared with 8% and 22%, respectively, in untreated mice. No significant impact of HBsAg level at baseline on response to TG1050 treatment was found. TG1050-treated mice displayed a significant shorter Time to Response (decline in viral parameters) with an Hazard Ratio (HR) of 8.3 for viremia and 2.6 for serum HBsAg. The mean predicted decrease for TG1050-treated mice was 0.5 log for viremia and 0.8 log for HBsAg, at the end of mice follow-up, compared to no decrease for viremia and 0.3 log HBsAg decrease for untreated mice. For mice receiving TG1050, a higher decline of circulating viremia and serum HBsAg level over time was detected by interaction term meta-analysis with a significant treatment effect (p = 0.002 and p |
| اللغة: | English |
| تدمد: | 2164-554X 2164-5515 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5cd74b4a1461fd543511de2ba9d47fcaTest http://europepmc.org/articles/PMC6037470Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5cd74b4a1461fd543511de2ba9d47fca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2164554X 21645515 |
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