Researchers found that treatment with a combination of Viread and GS-4774, a yeast-based therapeutic vaccine, increased hepatitis B-specific T cell immune response in untreated patients with chronic hepatitis B.
“HBV-specific T cells are deeply exhausted in untreated patients with chronic hepatitis B (CHB): reconstitution of their antiviral function represents a major goal of HBV immune therapies,” Carolina Boni, MD, from the University of Parma in Italy, and colleagues wrote. “Therapeutic compounds designed to restore an effective HBV-specific T-cell response represent promising tools for improving the rate of HBsAg loss and seroconversion in subjects with CHB compared with what is currently achievable with [nucleo(s)tide] alone.”
Boni and colleagues randomly assigned 195 patients to receive Viread (tenofovir disoproxil fumarate or TDF, Gilead Sciences) with GS-4774 (n = 168) or TDF alone (n = 27). While GS-4774 was originally engineered and evaluated to affect HBV surface antigen levels, the researchers found no significant differences between the two groups in HBsAg decline from baseline.
However, patients treated with the GS-4774 vaccine had significantly increased production of interferon gamma (IFNG), tumor necrosis factor (TNF) and interleukin 2 (IL2) by HBV-specific cytotoxic T cells at week 24 and week 48 compared with baseline. Patients treated with TDF alone showed no significant changes in immune response.
“Evolution of T-cell responses in patients treated with combined GS-4774 and tenofovir is well illustrated by hierarchical-clustering analysis of all data derived from all time points of therapy and from the reference acute hepatitis B control group for the definition of an efficient immune response able to control infection spontaneously,” the researchers wrote.
GS-4774 was generally well-tolerated. The most common treatment-emergent adverse events associated with injection site included pain, erythema and swelling, while other common events included fatigue and headache.
“Future combination therapies including vaccines should consider the sequential administration of drugs able to improve T-cell responsiveness to antigen stimulation by lowering the antigen load, such as, for example, silencing RNA compounds or capsid assembly inhibitors, or by inhibiting immune checkpoints or modulating T-cell metabolism, followed by T- and B-cell boosting through vaccination,” Boni and colleagues concluded. – by Talitha Bennett
Disclosure: The authors report no relevant financial disclosures.