Abstract

Background: We reported the HBsAg reduction by a nasal administrative therapeutic vaccine containing HBsAg/HBcAg mixed with mucoadhesive excipient carboxy-vinyl polymer (CVP-NASVAC) in chronically HBV infected patients. This study was aimed to assess the long-term efficacy of CVP-NASVAC at 48 months after the first 10 doses.

Methods: CHB patients were enrolled in an open-label clinical trial at Ehime University Hospital, Japan, after receiving written consent, and permission from institutional review board (CRB#18EC003), and registration to the clinical trial authority of Japan jRCT (#jRCTs061180100). CVP-NASVAC was administrated for 10 times, once in every 2 weeks, some patients received additional 10 doses at least 12 months interval. We analyzed the data at 48 months after the first 10 doses of CVP-NASVAC.

Results: Seventy-two patients enrolled in this study, and sixty-one participants completed 48 months follow-up and analyzed data. Twenty-five participants continued NAs during the study. Forty participants received additional 10 doses of CVP-NASVAC. At 48 months after the first 10 doses, 85.2% (n=52/61) patients showed HBsAg reduction from the baseline, and the mean HBsAg reduction was -40.3% (-0.4352 Log IU/mL). Notably, eight participants lost HBsAg. CVP-NASVAC induced anti-HBs in 70.5% (43/61) patients. HBcAg specific CTL were increased after the CVP-NASVAC treatment. Three out of nine patients lost HBeAg during 48 months follow-up. HBcrAg reduction was observed all the twenty-four participants who were detected HBcrAg at the baseline.

Conclusion: CVP-NASVAC displayed a long term HBsAg reduction and loss. CVP-NASVAC could be a novel immune therapy for HBsAg reduction and elimination in HBV infected patients.