April 12, 2019
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.
Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
EDITOR DISCLOSURES AT TIME OF PUBLICATION
Disclosures for Atif Zaman, MD, MPH at time of publication
Grant/Research Support Merck
Citation(s):
Boni C et al. Combined GS-4774 and tenofovir therapy can improve HBV-specific T-cell responses in patients with chronic hepatitis. Gastroenterology 2019 Mar 28; [e-pub]. (https://doi.org/10.1053/j.gastro.2019.03.044)作者: StephenW 时间: 2019-5-6 17:59