iScience. 2019 Oct 24;21:391-402. doi: 10.1016/j.isci.2019.10.040. [Epub ahead of print]
Virus-like Vesicles Expressing Multiple Antigens for Immunotherapy of Chronic Hepatitis B.
Yarovinsky TO1, Mason SW2, Menon M2, Krady MM2, Haslip M2, Madina BR2, Ma X2, Moshkani S3, Chiale C3, Pal AC4, Almassian B2, Rose JK4, Robek MD3, Nakaar V5.
Author information
1
CaroGen Corporation, Farmington, CT 06032, USA; Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: [email protected].
2
CaroGen Corporation, Farmington, CT 06032, USA.
3
Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
4
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
5
CaroGen Corporation, Farmington, CT 06032, USA. Electronic address: [email protected].
Abstract
Infections with hepatitis B virus (HBV) can initiate chronic hepatitis and liver injury, causing more than 600,000 deaths each year worldwide. Current treatments for chronic hepatitis B are inadequate and leave an unmet need for immunotherapeutic approaches. We designed virus-like vesicles (VLV) as self-amplifying RNA replicons expressing three HBV antigens (polymerase, core, and middle surface) from a single vector (HBV-VLV) to break immune exhaustion despite persistent HBV replication. The HBV-VLV induces HBV-specific T cells in naive mice and renders them resistant to acute challenge with HBV. Using a chronic model of HBV infection, we demonstrate efficacy of HBV-VLV priming in combination with DNA booster immunization, as 40% of treated mice showed a decline of serum HBV surface antigen below the detection limit and marked reduction in liver HBV RNA accompanied by induction of HBsAg-specific CD8 T cells. These results warrant further evaluation of HBV-VLV for immunotherapy of chronic hepatitis B.