Intranasal therapeutic vaccine containing HBsAg and HBcAg for patients with chronic hepatitis B; 18 months follow-up results of phase IIa clinical study |
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| Authors: | Osamu Yoshida Sheikh Mohammad Fazle Akbar Yusuke Imai Takahiro Sanada Kyoko Tsukiyama-Kohara Takashi Miyazaki Taizou Kamishita Teruki Miyake Yoshio Tokumoto Hayato Hikita Masataka Tsuge Masahito Shimizu Mamun Al Mahtab Julio Cesar Aguilar Gerardo Guillen Michinori Kohara Yoichi Hiasa |
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| Affiliation: | 1. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan;2. Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan;3. Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan;4. Toko Yakuhin Kogyo Co., Ltd, Osaka, Japan;5. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan;6. Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan;7. Department of Gastroenterology/Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan;8. Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh;9. Vaccine Division, Biomedical Research Department, Center for Genetic Engineering and Biotechnology, Havana City, Cuba |
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| Abstract: | ![]()
Aims HBsAg loss with anti-HBs acquisition is considered a functional cure and ideal treatment goal for patients with CHB. Our group have reported the efficacy of therapeutic vaccine with HBsAg and HBcAg (NASVAC) by intranasal and subcutaneous injection. In this study, we investigated the safety and efficacy of newly developed CVP-NASVAC, which contained NASVAC with mucoadhesive carboxyl vinyl polymer (CVP) in the dedicated device. Methods A single dose, open-label, phase IIa clinical trial of CVP-NASVAC was conducted. Patients with CHB treated with nucleoside/nucleotide analogs (NAs) and HBV carriers not undergoing anti-HBV treatment were enrolled. CVP-NASVAC was injected through the nose for, in total, 10 times. Participants were followed-up for 18 months, and their HBsAg reduction and anti-HBs induction assessed as endpoints. Results Among the patients with CHB treated with NAs (n = 27) and HBV carriers without NAs (n = 36), 74.1% and 75.0% exhibited reductions in their baseline HBsAg, and the mean reductions were −0.1454 log10 IU/ml (p < 0.05) and −0.2677 log10 IU/ml (p < 0.05), respectively. Anti-HBs antibody was detected in 40.7% and 58.3% of patients treated with and without NAs, respectively. Six of 71 (9.5%) patients were functionally cured after the CVP-NASVAC treatment. Conclusions Anti-HBs induction and HBsAg reduction was observed after CVP-NASVAC treatment in some patients with CHB. The CVP-NASVAC is a safe treatment, which might expect to achieve functional cure for patients with CHB. |
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| Keywords: | functional cure hepatitis B virus mucosal immunity nasal administration therapeutic vaccine |
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