用于慢性乙型肝炎患者的含 HBsAg 和 HBcAg 的鼻内治疗性疫苗；

StephenW

用于慢性乙型肝炎患者的含 HBsAg 和 HBcAg 的鼻内治疗性疫苗； IIa期临床研究18个月随访结果
Osamu Yoshida 1、Sheikh Mohammad Fazle Akbar 1、Yusuke Imai 1、Takahiro Sanada 2、Kyoko Tsukiyama-Kohara 3、Takashi Miyazaki 4、Taizou Kamishita 4、Teruki Miyake 1、Yoshio Tokumoto 1、Hayato Hikita 6 Tsuhige atmi、Tsuhita Makati atmi 5、 7、Mamun Al Mahtab 8、Julio Cesar Aguilar 9、Gerardo Guillen 9、Michinori Kohara 2、Yoichi Hiasa 1
隶属关系
隶属关系

    1个
    爱媛大学医学研究生院胃肠病学和代谢学系，Toon，爱媛，日本。
    2个
    日本东京都立医学科学研究所微生物学和细胞生物学系。
    3个
    日本鹿儿岛鹿儿岛大学兽医学院联合学院。
    4个
    Toko Yakuhin Kogyo Co., Ltd，日本大阪。
    5个
    日本大阪大阪大学医学研究生院胃肠病学和肝病学系。
    6个
    日本广岛广岛大学胃肠病学和新陈代谢系。
    7
    日本岐阜市岐阜大学医学研究生院消化内科/内科。
    8个
    Bangabandhu Sheikh Mujib 医科大学肝病学系，孟加拉国达卡。
    9
    古巴哈瓦那市基因工程和生物技术中心生物医学研究部疫苗部。

    PMID：36399406 DOI：10.1111/hepr.13851

抽象的

目的：获得抗 HBs 后 HBsAg 消失被认为是 CHB 患者的功能性治愈和理想治疗目标。我们的小组已经报道了通过鼻内和皮下注射使用 HBsAg 和 HBcAg (NASVAC) 的治疗性疫苗的功效。在这项研究中，我们调查了新开发的 CVP-NASVAC 的安全性和有效性，该 CVP-NASVAC 在专用设备中包含带有粘膜粘附羧基乙烯基聚合物 (CVP) 的 NASVAC。

方法：进行了 CVP-NASVAC 的单剂量、开放标签、IIa 期临床试验。接受核苷/核苷酸类似物 (NAs) 治疗的 CHB 患者和未接受抗 HBV 治疗的 HBV 携带者被纳入。 CVP-NASVAC 经鼻注射，共 10 次。对参与者进行了 18 个月的随访，并将他们的 HBsAg 降低和抗 HBs 诱导作为终点进行评估。

结果：在接受 NA 治疗的 CHB 患者（n = 27）和未接受 NA 治疗的 HBV 携带者（n = 36）中，74.1% 和 75.0% 的基线 HBsAg 有所降低，平均降低为 -0.1454 log10 IU/ml（ p < 0.05) 和 -0.2677 log10 IU/ml (p < 0.05)。在接受和未接受 NAs 治疗的患者中，分别有 40.7% 和 58.3% 检测到抗 HBs 抗体。 71 名患者中有 6 名 (9.5%) 在 CVP-NASVAC 治疗后获得功能性治愈。

结论：部分 CHB 患者在 CVP-NASVAC 治疗后观察到抗 HBs 诱导和 HBsAg 降低。 CVP-NASVAC 是一种安全的治疗方法，有望实现 CHB 患者的功能性治愈。

关键词：功能性治愈；乙型肝炎病毒;粘膜免疫；鼻腔给药；治疗性疫苗。

© 2022 作者。 Hepatology Research 由 John Wiley & Sons Australia, Ltd 代表日本肝病学会出版。

StephenW

Intranasal therapeutic vaccine containing HBsAg and HBcAg for patients with chronic hepatitis B; 18 months follow-up results of phase IIa clinical study
Osamu Yoshida  1 , Sheikh Mohammad Fazle Akbar  1 , Yusuke Imai  1 , Takahiro Sanada  2 , Kyoko Tsukiyama-Kohara  3 , Takashi Miyazaki  4 , Taizou Kamishita  4 , Teruki Miyake  1 , Yoshio Tokumoto  1 , Hayato Hikita  5 , Masataka Tsuge  6 , Masahito Shimizu  7 , Mamun Al Mahtab  8 , Julio Cesar Aguilar  9 , Gerardo Guillen  9 , Michinori Kohara  2 , Yoichi Hiasa  1
Affiliations
Affiliations

    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.

    PMID: 36399406 DOI: 10.1111/hepr.13851

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.

Keywords: functional cure; hepatitis B virus; mucosal immunity; nasal administration; therapeutic vaccine.

© 2022 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.