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bioRxiv · 10.1101/2025.02.12.636533

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

Limeres, M. J.·Gambaro, R.·Svensson, M.·Fraude-El Ghazi, S.·Pretsch, L.·Frank, D.·Islan, G. A.·Rivero Berti, I.·Bros, M.·Tam, Y. K.·Muramatsu, H.·Pardi, N.·Gehring, S.·Cacicedo, M. L.
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Abstract

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.

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Limeres, M. J., Gambaro, R., Svensson, M., Fraude-El Ghazi, S., Pretsch, L., Frank, D., Islan, G. A., Rivero Berti, I., Bros, M., Tam, Y. K., Muramatsu, H., Pardi, N., Gehring, S., Cacicedo, M. L.. 2025-02-14. mRNA-LNP vaccines against Hepatitis B virus induce protective immune responses in preventive and chronic mouse challenge models. https://doi.org/10.1101/2025.02.12.636533

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