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
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 immunotherap...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-06-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2018.1433970 |
| _version_ | 1797677507798892544 |
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| author | Roland Kratzer Benoît Sansas Karine Lélu Alexei Evlachev Doris Schmitt Nathalie Silvestre Geneviève Inchauspé Perrine Martin |
| author_facet | Roland Kratzer Benoît Sansas Karine Lélu Alexei Evlachev Doris Schmitt Nathalie Silvestre Geneviève Inchauspé Perrine Martin |
| author_sort | Roland Kratzer |
| collection | DOAJ |
| description | 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, 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<0.001 respectively). This meta-analysis confirms the therapeutic value of TG1050, capable of exerting potent antiviral effects in an HBV-persistent model mimicking clinical situations. |
| first_indexed | 2024-03-11T22:46:13Z |
| format | Article |
| id | doaj.art-e396c2e09f3f455183af950de311beb9 |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:46:13Z |
| publishDate | 2018-06-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-e396c2e09f3f455183af950de311beb92023-09-22T08:17:54ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2018-06-011461417142210.1080/21645515.2018.14339701433970A 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 modelRoland Kratzer0Benoît Sansas1Karine Lélu2Alexei Evlachev3Doris Schmitt4Nathalie Silvestre5Geneviève Inchauspé6Perrine Martin7Transgene SA, Dept. of Infectious DiseasesTransgene SA, Smart Data LabTransgene SA, Dept. of Infectious DiseasesTransgene SA, Dept. of Infectious DiseasesTransgene SA, Smart Virus LabTransgene SA, Smart Virus LabTransgene SA, Dept. of Infectious DiseasesTransgene SA, Dept. of Infectious DiseasesPre-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, 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<0.001 respectively). This meta-analysis confirms the therapeutic value of TG1050, capable of exerting potent antiviral effects in an HBV-persistent model mimicking clinical situations.http://dx.doi.org/10.1080/21645515.2018.1433970aav-hbv mouse modelchronic hepatitis bimmunotherapeuticmeta-analysistg1050 |
| spellingShingle | Roland Kratzer Benoît Sansas Karine Lélu Alexei Evlachev Doris Schmitt Nathalie Silvestre Geneviève Inchauspé Perrine Martin 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 Human Vaccines & Immunotherapeutics aav-hbv mouse model chronic hepatitis b immunotherapeutic meta-analysis tg1050 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | aav-hbv mouse model chronic hepatitis b immunotherapeutic meta-analysis tg1050 |
| url | http://dx.doi.org/10.1080/21645515.2018.1433970 |
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