Chronic Hepatitis B Virus (HBV)

Virion has developed a series of novel vaccine candidates for chronic HBV infection that couple key regions of the HBV virus with our genetically encoded checkpoint inhibitor, gD. Preclinical data have shown these vaccines to produce highly potent and durable HBV-specific T cell responses and when given alone as a single intramuscular injection in preclinical studies, multi-log, sustained HBV viral load reductions. These data are the first immune- or T cell-based treatments to show such results (see more) and are consistent with gD’s mechanism of action which broadens and enhances T cell recognition to include sub-dominant epitopes, which are more resistant to exhaustion. VRON-0200 could be a foundational component of multi-modal therapies for HBV functional cure. 

 

Worldwide, infection with Hepatitis B virus (HBV) results in an estimated 900,000 deaths/year. Among patients unable to clear the virus on their own (over 257 million persons globally), HBV infects the liver and causes tissue damage, inflammation and over time cirrhosis, liver cancer and possibly death. In addition, chronic HBV infection produces high levels of virus particles which causes CD8+ T cell exhaustion. Current treatment consists of the administration of antiviral agents that suppress viral replication thereby preventing continued infection and destruction of the liver; this strategy, however, does not suppress viral particle production or reverses T cell exhaustion and therefore patients are required to take these agents for life.

 

A number of investigational treatments are in development which inhibit both viral replication and particle production with the goal of restoring immune functions so that patients can control the infection on their own without the need for antiviral therapy. Some companies are also combining these therapies with a therapeutic vaccine aimed at stimulating HBV-specific T cells. It is unknown if these combinations will stimulate a sufficient CD8+ T cell response. Data from other chronic viral infections have shown shifts in T cell recognition patterns from areas of high recognition (aka dominant epitopes), which can become rapidly exhausted, to regions that are not as highly recognized (aka, sub-dominant epitopes) and more resistant to exhaustion. If this shift occurs in chronic HBV, vaccines that stimulate CD8+ T cells to dominant epitopes may produce inadequate immune responses upon treatment discontinuation resulting in viral and particle rebound.