Novel vaccine passes phase II trial in virally suppressed CHB

Therapeutic vaccination with ChAdOx1-HBV/MVA-HBV (VTP-300) has generated CD4+ and CD8+ cells and reduced HBsAg in a subset of chronic hepatitis B (CHB) patients with baseline values <100 IU/ml, as shown in a phase Ib/IIa trial. Moreover, a significant decrease in surface antigen occurs when the vaccine is combined with low-dose nivolumab.

A team of investigators examined a chimpanzee adenoviral vector (ChAdOx1-HBV) and a Modified vaccinia Ankara boost (MVA-HBV) encoding the inactivated polymerase, core, and S region from a consensus genotype C hepatitis B virus (HBV). They enrolled 55 patients with virally suppressed CHB and HBsAg <4,000 IU/ml and divided them into four groups.

Group 1 received MVA-HBV intramuscularly on day 0 and day 28, group 2 received ChAdOx1-HBV on day 0 and MVA-HBV on day 28 (VTP-300), group 3 received VTP-300 plus low-dose nivolumab on day 28, and group 4 received VTP-300 plus low-dose nivolumab with both injections.

VTP-300, whether alone or in combination with nivolumab, had good tolerability and did not result in any serious treatment-related adverse events.

Group 2 showed reductions in HBsAg, with three of 18 patients with starting HBsAg <50 IU/ml exhibiting durable log10 declines of >0.7 log10 at 2 months after the last dose. Group 3 patients also demonstrated reductions in HBsAg, with a mean of 0.76 and 0.80 log10 at 2 and 7 months, respectively, after the last dose (p<0.001).

VTP-300 induced CD4+ and CD8+ antigen-specific T-cell responses. Moreover, investigators observed an association between IFN-γ ELISpot response and HBsAg decline in group 2.

“VTP-300 is a promising immunotherapeutic that warrants further development alone or in combination therapies,” the investigators said.