1Department of Infectious Diseases, Transgene SA, Lyon, France
2Laboratoire de pathogénèse des virus de l'hépatite B Paris and INSERM U994, Institut Pasteur, Paris, France
3Virology Unit, Cochin Hospital, Paris, France
4Department of Vectors, Transgene SA, Strasbourg, France
5Laboratoire de Spectrométrie de Masse BioOrganique, Strasbourg University, UMR 7178, Strasbourg, France
Correspondence to Dr Geneviève Inchauspé, Transgene SA, 321 Avenue Jean Jaures, Lyon 69007, France; [email protected]
Received 15 July 2014
Revised 4 October 2014
Accepted 20 October 2014
Published Online First 26 November 2014
Abstract
Objective To assess a new adenovirus-based immunotherapy as a novel treatment approach to chronic hepatitis B (CHB).
Methods TG1050 is a non-replicative adenovirus serotype 5 encoding a unique large fusion protein composed of a truncated HBV Core, a modified HBV Polymerase and two HBV Envelope domains. We used a recently described HBV-persistent mouse model based on a recombinant adenovirus-associated virus encoding an over length genome of HBV that induces the chronic production of HBsAg, HBeAg and infectious HBV particles to assess the ability of TG1050 to induce functional T cells in face of a chronic status.
Results In in vitro studies, TG1050 was shown to express the expected large polyprotein together with a dominant, smaller by-product. Following a single administration in mice, TG1050 induced robust, multispecific and long-lasting HBV-specific T cells detectable up to 1 year post-injection. These cells target all three encoded immunogens and display bifunctionality (ie, capacity to produce both interferon γ and tumour necrosis factor α as well as cytolytic functions). In addition, control of circulating levels of HBV DNA and HBsAg was observed while alanine aminotransferase levels remain in the normal range.
Conclusions Injection of TG1050 induced both splenic and intrahepatic functional T cells producing cytokines and displaying cytolytic activity in HBV-naïve and HBV-persistent mouse models together with significant reduction of circulating viral parameters. These results warrant clinical evaluation of TG1050 in the treatment of CHB.
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
这是分布在依照知识共享署名非商业(CC BY-NC 4.0)的许可证,允许他人分发,混音,改编,建立在这项工作中的非商业化,并授权他们在不同的衍生作品的开放存取的文章术语,提供的原始工作正确的引用和使用是非商业。请参阅:http://creativecommons.org/licenses/by-nc/4.0/
Google Translate for Business:Translator ToolkitWebsite TranslatorGlobal Marke