Virus-like Vesicles Expressing Multiple Antigens for Immunotherapy of Chronic Hepatitis B

• Main Authors: Timur O. Yarovinsky, Stephen W. Mason, Manisha Menon, Marie M. Krady, Maria Haslip, Bhaskara R. Madina, Xianyong Ma, Safiehkhatoon Moshkani, Carolina Chiale, Anasuya Chattopadhyay Pal, Bijan Almassian, John K. Rose, Michael D. Robek, Valerian Nakaar
• Format: Article
• Language: English
• Published: Elsevier 2019-11-01
• Series: iScience
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004219304201

Summary: 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. : Immunology; Virology; Medical Microbiology Subject Areas: Immunology, Virology, Medical Microbiology