mRNA-LNP vaccines against Hepatitis B virus induce protective immune responses in preventive and chronic mouse challenge models

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Detalles Bibliográficos
Publicado en:	bioRxiv (Feb 14, 2025)
Autor principal:	Limeres, Maria Jose
Otros Autores:	Gambaro, Rocio, Svensson, Malin, Silvia Fraude-El Ghazi, Pretsch, Leah, Frank, Daniel, Islan, German A, Ignacio Rivero Berti, Bros, Matthias, Tam, Ying K, Muramatsu, Hiromi, Pardi, Norbert, Gehring, Stephan, Cacicedo, Maximiliano L
Publicado:	Cold Spring Harbor Laboratory Press
Materias:	BioNTech SE Infections Prophylaxis Vaccines Immune clearance Nanoparticles Hepatocellular carcinoma Patent applications mRNA Lymphocytes T Chronic illnesses Hepatitis B surface antigen Chronic infection Immune response (humoral) Nucleosides Major histocompatibility complex Immune system Animal models Immune response (cell-mediated) Seroconversion Hepatitis B Therapeutic applications
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Descripción
Resumen:	Over 300 million people worldwide suffer from chronic hepatitis B virus infections that can cause serious liver damage and hepatocellular carcinoma. Ineffective innate and adaptive immune responses characterize these chronic infections, making the development of a therapeutic vaccine an urgent medical need. While current vaccines can prevent HBV infections, they are ineffective in treating chronic disease. This study investigated lipid nanoparticle (LNP)-formulated nucleoside-modified mRNA vaccines encoding Hepatitis B surface antigen (HBsAg) for prophylactic and therapeutic applications. We found that HBsAg mRNA-LNP vaccines induced robust humoral and cellular immune responses, outperforming the protein-based vaccine approved for human use. The incorporation of an MHC class I signal peptide further enhanced Th1-biased responses preventing HBV infections in a mouse model. Importantly, mRNA-LNP vaccination led to seroconversion, HBsAg clearance, and strong T cell responses in a chronically infected mouse model. These findings highlight the potential of mRNA-LNP as an alternative and effective vaccine modality for HBV prophylaxis and therapeutic use in treating chronic infections.Competing Interest StatementM.L.C. is currently an employee at BioNTech SE (Mainz, Germany), however, the contributions from M.L.C. were made prior to his employment at BioNTech SE. The company had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. N.P., M.L.C., M.J.L. and S.G. have a provisional patent application that describes the use of nucleoside-modified mRNA in lipid nanoparticles to treat and/or prevent HBV infections. The remaining authors declare no conflict of interest.
ISSN:	2692-8205
DOI:	10.1101/2025.02.12.636533
Fuente:	Biological Science Database