用含有HBs和HBc抗原的治疗性疫苗治疗慢性乙型肝炎初治患者

StephenW

PLoS One. 2018 Aug 22;13(8):e0201236. doi: 10.1371/journal.pone.0201236. eCollection 2018.
Treatment of chronic hepatitis B naïve patients with a therapeutic vaccine containing HBs and HBc antigens (a randomized, open and treatment controlled phase III clinical trial).
Al Mahtab M1, Akbar SMF2, Aguilar JC3, Guillen G3, Penton E3, Tuero A3, Yoshida O4, Hiasa Y4, Onji M5.
Author information

1
    Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.
2
    Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan.
3
    Department of Biomedical Research, Center for Genetic Engineering and Biotechnology, Havana, Cuba.
4
    Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
5
    Department of Medicine, Sai Sei Kai Imabari Hospital, Imabari, Japan.

Abstract
CONTEXT:

Current drugs for chronic hepatitis B therapy have a poor efficacy in terms of post-treatment sustained viral suppression and generate important side effects during and after therapy. Therapeutic vaccination with HBV antigens is an attractive alternative to test.
OBJECTIVE:

Evaluating the efficacy of a therapeutic vaccine candidate (designated NASVAC) containing both hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) versus pegylated interferon (Peg-IFN) in naïve chronic hepatitis B patients.
DESIGN, SETTING, PARTICIPANTS:

An open phase III, randomised and treatment controlled clinical trial was conducted in a total of 160 CHB patients, allocated into two groups of 80 patients each to receive NASVAC or Peg-IFN. The vaccine formulation comprised 100 μg of each HBsAg and HBcAg, and was administered in 2 cycles of 5 doses. The control group received 48 subcutaneous injections of Peg-IFN alfa 2b, 180 μg per dose, every week, for 48 consecutive weeks.
MAIN OUTCOME MEASURE:

The primary outcome measure was in relation with the proportion of patients showing reduction of the viral load under the limit of detection (250 copies/mL) after 24 weeks of treatment completion.
RESULTS:

Sustained control of HBV DNA was significantly more common in NASVAC group (p<0.05) at 24 weeks of follow up. NASVAC-induced increases of alanine aminotransferases (ALT) were detected in 85% patients after 5 nasal vaccinations, although seen in only 30% of patients receiving Peg-IFN. At the end of treatment (EOT) antiviral effect was comparable in both NASVAC and Peg-IFN groups. Clearance of Hepatitis B e antigen (HBeAg) was also more frequent in NASVAC group compared to Peg-IFN recipients. A lower progression to cirrhosis was found in NASVAC group compared to Peg-IFN group.
CONCLUSION:

Nasvac induced a superior reduction of the viral load under the limit of detection compared to Peg-IFN treatment. It is a safe and efficacious finite alternative of antiviral treatment for CHB patients.
TRIAL REGISTRATION:

ClinicalTrials.gov NCT 01374308.

PMID:
    30133478
DOI:
    10.1371/journal.pone.0201236

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StephenW

PLoS One。 2018年8月22日; 13（8）：e0201236。 doi：10.1371 / journal.pone.0201236。 eCollection 2018。
用含有HBs和HBc抗原的治疗性疫苗治疗慢性乙型肝炎初治患者（随机，开放和治疗控制的III期临床试验）。
Al Mahtab M1，Akbar SMF2，Aguilar JC3，Guillen G3，Penton E3，Tuero A3，Yoshida O4，Hiasa Y4，Onji M5。
作者信息

1
孟加拉国达卡Bangabandhu Sheikh Mujib医科大学肝病学系。
2
日本东京东芝总医院医学科学系。
3
古巴哈瓦那基因工程和生物技术中心生物医学研究系。
4
爱媛大学大学院医学研究科消化内科，日本爱媛县。
五
日本今治西赛凯今治医院医学系。

抽象
背景：

目前用于慢性乙型肝炎治疗的药物在治疗后持续病毒抑制方面效果差，并且在治疗期间和治疗后产生重要的副作用。用HBV抗原进行的治疗性疫苗接种是测试的有吸引力的替代方案。
目的：

评估在初治慢性乙型肝炎患者中含有乙型肝炎表面抗原（HBsAg）和核心抗原（HBcAg）与聚乙二醇化干扰素（Peg-IFN）的治疗性候选疫苗（命名为NASVAC）的功效。
设计，设置，参与者：

在总共160名CHB患者中进行开​​放III期随机和治疗对照临床试验，分成两组，每组80名患者接受NASVAC或Peg-IFN。疫苗制剂包含100μg的每种HBsAg和HBcAg，并以5个剂量的2个循环施用。对照组每周接受48次皮下注射Peg-IFNα2a，每剂180μg，持续48年。
主要观察指标：

主要结局指标与治疗完成24周后检测限（250拷贝/ mL）下病毒载量降低的患者比例有关。
结果：

在随访24周时，NASVAC组中HBV DNA的持续控制显着更常见（p <0.05）。在5次鼻疫苗接种后，85％的患者检测到NASVAC诱导的丙氨酸氨基转移酶（ALT）增加，尽管只有30％的患者接受Peg-IFN。在治疗结束时（EOT），NASVAC和Peg-IFN组的抗病毒效果相当。与Peg-IFN受体相比，NASVAC组中乙型肝炎e抗原（HBeAg）的清除率也更高。与Peg-IFN组相比，在NASVAC组中发现较低的肝硬化进展。
结论：

与Peg-IFN处理相比，Nasvac在检测限下诱导了病毒载量的优异降低。对于CHB患者，它是一种安全有效的抗病毒治疗替代方案。
试用注册：

ClinicalTrials.gov NCT 01374308。

结论：
30133478
DOI：
10.1371 / journal.pone.0201236

StephenW

http://journals.plos.org/plosone ... ournal.pone.0201236