Dual-targeting nanoparticle vaccine elicits a therapeutic antibody response against chronic hepatitis B
Chronic hepatitis B is caused by prolonged infection with the hepatitis B virus (HBV), which can substantially increase the risk of developing liver disease. Despite the development of preventive vaccines against HBV, a therapeutic vaccine inducing an effective antibody response still remains elusiv...
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Veröffentlicht in: | Nature nanotechnology 2020-05, Vol.15 (5), p.406-416 |
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Sprache: | eng |
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Zusammenfassung: | Chronic hepatitis B is caused by prolonged infection with the hepatitis B virus (HBV), which can substantially increase the risk of developing liver disease. Despite the development of preventive vaccines against HBV, a therapeutic vaccine inducing an effective antibody response still remains elusive. The preS1 domain of the large HBV surface protein is the major viral attachment site on hepatocytes and thus offers a therapeutic target; however, its poor immunogenicity limits clinical translation. Here, we design a ferritin nanoparticle vaccine that can deliver preS1 to specific myeloid cells, including SIGNR1
+
dendritic cells (which activate T follicular helper cells) and lymphatic sinus-associated SIGNR1
+
macrophages (which can activate B cells). This nanoparticle vaccine induces a high-level and persistent anti-preS1 response that results in efficient viral clearance and partial serological conversion in a chronic HBV mouse model, offering a promising translatable vaccination strategy for the functional cure of chronic hepatitis B.
A ferritin nanoparticle that delivers the preS1 domain of the large hepatitis B surface protein to two specific myeloid cell populations provides a therapeutic vaccination strategy for the treatment of chronic hepatitis B. |
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ISSN: | 1748-3387 1748-3395 |
DOI: | 10.1038/s41565-020-0648-y |