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

Artículo

Autoría
Limeres, María José ; Gambaro, Rocio ; Svensson, Malin ; Fraude-El Ghazi, Silvia ; Pretsch, Leah ; Frank, Daniel ; ISLAN, GERMAN ABEL ; Berti, Ignacio Rivero ; Bros, Matthias ; Tam, Ying K. ; Muramatsu, Hiromi ; Pardi, Norbert ; Gehring, Stephan ; Cacicedo, Maximiliano L.
Fecha
2025
Editorial y Lugar de Edición
NATURE PUBLISHING GROUP
Revista
MOLECULAR THERAPY (PRINT), vol. 33 (pp. 4156-4174) NATURE PUBLISHING GROUP
Resumen Información suministrada por el agente en SIGEVA
Over 300 million people worldwide suffer from chronic hepatitis B virus (HBV) 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 mRN... Over 300 million people worldwide suffer from chronic hepatitis B virus (HBV) 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 a major histocompatibility complex class I (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.
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Palabras Clave
Hepatitis B VirusHBsAgChronic hepatitis BmRNA-LNP vaccineIVT mRNA