Virus-like Vesicles Expressing Multiple Antigens for Immunotherapy of Chronic Hepatitis B
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
Affiliations
Timur O. Yarovinsky
CaroGen Corporation, Farmington, CT 06032, USA; Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA; Corresponding author
Stephen W. Mason
CaroGen Corporation, Farmington, CT 06032, USA
Manisha Menon
CaroGen Corporation, Farmington, CT 06032, USA
Marie M. Krady
CaroGen Corporation, Farmington, CT 06032, USA
Maria Haslip
CaroGen Corporation, Farmington, CT 06032, USA
Bhaskara R. Madina
CaroGen Corporation, Farmington, CT 06032, USA
Xianyong Ma
CaroGen Corporation, Farmington, CT 06032, USA
Safiehkhatoon Moshkani
Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA
Carolina Chiale
Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA
Anasuya Chattopadhyay Pal
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA
Bijan Almassian
CaroGen Corporation, Farmington, CT 06032, USA
John K. Rose
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA
Michael D. Robek
Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA
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
