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P08

Generation of mRNA-based therapeutic vaccines against chronic HBV infection

S Singh(2) E Ates Öz(2) A Kosinska(1,2) U Protzer(1,2)

1:German Centre for Infection research (DZIF), Munich partner site, 8675, Munich, Germany; 2:Institute of Virology, School of Medicine and Health, Technical University of Munich/Helmholtz Munich, 81675, Munich, Germany

Despite the availability of the prophylactic vaccine, hepatitis B virus (HBV) infection remains a major global public health concern, with over 250 million people chronically infected and 1.1 million deaths each year. Scarce and impaired virus-specific CD8+ T-cell responses mark a chronic HBV infection. Inducing HBV-specific immunity by therapeutic vaccination has the potential to break HBV-specific immune tolerance and cure chronic infection. Recent advancements in mRNA vaccine technology suggest this could be a promising approach for therapeutic vaccination. The main objective of this study is the development and characterization of a potent mRNA vaccine encoding major HBV epitopes. These epitopes were selected based on the most prevalent genotypes, A-E, covering 95% of globally circulating HBV strains. We characterized various structural elements of mRNA to assess their impact on stability, translatability, and half-life in an in-vitro system. We demonstrated that incorporating untranslated regions (5' and 3' UTRs), 5' capping, Poly-A tailing, and chemical modifications significantly enhanced the potency of the mRNA generated. In the next steps, we aim to evaluate the impact of these modifications on reactogenicity against our candidate mRNAs. Consequently, we aim to develop and characterize various delivery formulations that effectively deliver our mRNA vaccine in vivo. Our ultimate goal is to assess our mRNA vaccine's ability to elicit strong and multi-specific T-cell responses, resulting in robust antiviral effects in a mouse model of persistent HBV infection.

Sekretariat der DG-GT e.V.
Institut für Experimentelle Hämatologie
Hildegard Büning
Carl-Neuberg-Str. 1
30625 Hannover

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© 2021 Die Deutsche Gesellschaft für Gentherapie e.V.

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