Science and Technology Production
Article
Authorship
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.
Date
2025
Publishing House and Editing Place
NATURE PUBLISHING GROUP
Magazine
MOLECULAR THERAPY (PRINT),
vol. 33
(pp. 4156-4174)
NATURE PUBLISHING GROUP
Summary
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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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Key Words
Hepatitis B VirusHBsAgChronic hepatitis BmRNA-LNP vaccineIVT mRNA