双剂量研究性乙型肝炎疫苗HBsAg-1018在成人中使用toll样受体9

StephenW

Vaccine. 2018 Apr 5. pii: S0264-410X(18)30436-5. doi: 10.1016/j.vaccine.2018.03.067. [Epub ahead of print]
Safety of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant in adults.Hyer R1, McGuire DK2, Xing B1, Jackson S3, Janssen R4.
Author information
1Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, CA 94710, United States.2University of Texas-Southwestern Medical Center, 5939 Harry Hines Blvd #935, Dallas, TX 75235, United States.3Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, CA 94710, United States. Electronic address: [email protected].4Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, CA 94710, United States. Electronic address: [email protected].

AbstractBACKGROUND: Hepatitis B virus infection remains an important global public health problem. Approved alum-adjuvanted vaccines are well tolerated but require three doses and have reduced immunogenicity in adults. A two-dose vaccine containing hepatitis B surface antigen combined with a novel, Toll-like receptor 9 agonist adjuvant (HBsAg-1018 [HEPLISAV-B®]) has demonstrated significantly higher seroprotection rates than a three dose vaccine.
METHODS: A post hoc analysis compared the safety of HBsAg-1018 with HBsAg-Eng (Engerix-B®), in three randomized, observer-blinded, active-controlled, multi-center phase 3 trials in adults. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24.
RESULTS: Post-injection reactions, adverse events, medically attended adverse events, and new-onset immune-mediated adverse events were balanced between vaccine groups. Anti-nuclear antibodies, anti-double stranded DNA antibodies, anti-neutrophil cytoplasmic antibodies, and antiphospholipid antibodies were balanced between groups. A transient increase in anti-beta2 glycoprotein 1 IgM was observed in the HBsAg-1018 group but was not associated with a thrombotic event. Serious adverse events and deaths were generally balanced between groups.
CONCLUSION: HBsAg-1018 had a similar safety profile to HBsAg-Eng. With improved immunogenicity and fewer doses over a shorter time, HBsAg-1018 has the potential to provide improved seroprotection and a significant public health benefit to adults 18 years of age or older.

Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

KEYWORDS: Hepatitis B vaccine; NCT00435812; NCT01005407; NCT02117934; Safety; Toll-like receptor 9

PMID:29628151DOI:10.1016/j.vaccine.2018.03.067

StephenW

疫苗。 2018年4月5日，pii：S0264-410X（18）30436-5。 doi：10.1016 / j.vaccine.2018.03.067。 [电子版提前打印]
双剂量研究性乙型肝炎疫苗HBsAg-1018在成人中使用toll样受体9激动剂佐剂的安全性。
Hyer R1，McGuire DK2，Xing B1，Jackson S3，Janssen R4。
作者信息

1
    Dynavax Technologies Corporation，2929 Seventh Street，Suite 100，Berkeley，CA 94710，美国。
2
    德克萨斯大学西南医学中心，5939哈利海恩斯大道＃935，达拉斯，TX 75235，美国。
3
    Dynavax Technologies Corporation，2929 Seventh Street，Suite 100，Berkeley，CA 94710，美国。电子地址：[email protected]。
4
    Dynavax Technologies Corporation，2929 Seventh Street，Suite 100，Berkeley，CA 94710，美国。电子地址：[email protected]。

抽象
背景：

乙型肝炎病毒感染仍然是一个重要的全球公共卫生问题。批准的明矾佐剂疫苗耐受性良好，但需要三剂，并且在成人中具有降低的免疫原性。含有乙型肝炎表面抗原和Toll样受体9激动剂佐剂（HBsAg-1018 [HEPLISAV-B®]）的两剂疫苗与三剂疫苗相比显示出显着更高的血清保护率。
方法：

事后分析比较了HBsAg-1018与HBsAg-Eng（Engerix-B®）在三项随机，观察者盲法，主动控制，多中心的成人3期临床试验中的安全性。在第0周和第4周肌内注射HBsAg-1018，在第24周注射安慰剂，在第0,4和24周注射HBsAg-Eng。
结果：

疫苗组之间的注射后反应，不良事件，医学上不良事件和新发免疫介导的不良事件均衡。抗核抗体，抗双链DNA抗体，抗嗜中性粒细胞胞质抗体和抗磷脂抗体在组间平衡。在HBsAg-1018组中观察到抗β2糖蛋白1 IgM短暂增加，但与血栓事件无关。各组之间的严重不良事件和死亡总体平衡。
结论：

HBsAg-1018与HBsAg-Eng具有相似的安全性。随着免疫原性的提高和更短时间内的剂量减少，HBsAg-1018有可能为18岁或以上的成年人提供改善的血清保护作用和显着的公共健康益处。

版权所有©2018 The Author（s）。由Elsevier Ltd出版。保留所有权利。
关键词：

乙型肝炎疫苗; NCT00435812; NCT01005407; NCT02117934;安全; Toll样受体9

结论：
    29628151
DOI：
    10.1016 / j.vaccine.2018.03.067