Tenofovir Disoproxil Fumarate plus a Therapeutic Vaccine for Chronic HBV Infection
Atif Zaman, MD, MPH reviewing Boni C et al. Gastroenterology 2019 Mar 28
Adding investigational vaccine GS-4775 activated immune response but did not reduce hepatitis B surface antigen levels.
Current treatment modalities cannot cure hepatitis B virus (HBV) infection. There has been some hope that adding adjunctive therapies to available direct-acting antiviral agents could stimulate HBV-specific T-cell responses that could ultimately lead to cure.
In an industry-funded, phase II, open-label study, researchers evaluated the safety and efficacy of adding GS-4774, a yeast-based therapeutic vaccine that expresses HBV antigens, to tenofovir disoproxil fumarate (TDF) in treatment-naive HBV-infected patients. Patients with HBV DNA ≥2000 IU/mL were randomized in a 1:2:2:2 fashion to receive daily TDF 300 mg alone (n=27) or in combination with 2, 10, or 40 GS-4774 yeast units, given subcutaneously every 4 weeks until week 20 (n=168).
The primary efficacy endpoint, reduction in hepatitis B surface antigen (HBsAg) levels from baseline to week 24, was not greater with addition of GS-4774. Although patients receiving the highest GS-4774 dose had the greatest HBsAg decline, it was not significantly different compared with the TDF-only group. Only a small proportion of patients receiving GS-4774 demonstrated a ≥0.5 log10 IU/mL decline in HBsAg level. In a small subgroup analysis of HBeAg-negative patients, those that received GS-4774 had increased production of tumor necrosis factor, interleukin 2, and interferon gamma by CD8+ T cells exposed to antigenic peptides but did not have increased CD4+ T cell production.
Comment
Although the use of a therapeutic vaccine with a direct-acting antiviral agent induced an immune response in these HBV-infected patients, it did not reduce HBsAg levels. This is likely due to the lack of CD4+ T cell induction. I expect to see continued research on therapeutic vaccines as part of an anti-HBV treatment regimen that ultimately may be curative. 作者: StephenW 时间: 2019-4-13 16:00