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

iScience, ISSN: 2589-0042, Vol: 21, Page: 391-402
2019
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Article Description

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.

Bibliographic Details

Yarovinsky, Timur O; Mason, Stephen W; Menon, Manisha; Krady, Marie M; Haslip, Maria; Madina, Bhaskara R; Ma, Xianyong; Moshkani, Safiehkhatoon; Chiale, Carolina; Pal, Anasuya Chattopadhyay; Almassian, Bijan; Rose, John K; Robek, Michael D; Nakaar, Valerian

Elsevier BV

Multidisciplinary

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