Advantages to the use of rodent hepadnavirus core proteins as vaccine platforms
Advantages to the use of rodent hepadnavirus core proteins as vaccine platforms
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DOI：
10.1016/j.vaccine.2006.11.013
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发表时间：
2007-02-19
期刊：
影响因子：
5.5
通讯作者：
Milich, David
中科院分区：
文献类型：
--
作者：
Billaud, Jean-Noel;Peterson, Darrell;Milich, David
已提出将肝炎B核心抗原（HBcAg）作为免疫原性差的肽和碳水化合物B细胞表位的有用颗粒载体平台。然而.生物化学和免疫学障碍困扰着这种技术。具体地，以由外源序列的插入导致的不稳定杂交颗粒的低产率为特征的“组装”问题和由于HBcAg来源于人类病原体的事实而导致的“预先存在的免疫”问题限制了这种载体技术的发展。作为解决“预先存在的免疫”问题的手段，我们使用了来自啮齿动物hepdnaviruses的核心蛋白。与HBcAg相比，使用啮齿动物嗜肝DNA病毒核心蛋白用于疫苗设计的许多优点被定义，包括：在T和B细胞水平上具有相等或上级的免疫原性，使用啮齿动物核心蛋白不损害抗-HBc诊断测定;啮齿动物核心蛋白作为疫苗载体的功效将不受预先存在的抗-存在于先前和当前HBV感染者中的HBc抗体;以及存在于HBV慢性携带者中的HBcAg特异性耐受性可以通过使用啮齿动物核心蛋白来规避。(c)2006爱思唯尔有限公司保留所有权利。
The hepatitis B core antigen (HBcAg) has been proposed as a useful particulate carrier platform for poorly immunogenic peptidic and carbohydrate B cell epitopes. However. biochemical and immunologic impediments have plagued this technology. Specifically, the "assembly" problem characterized by the low yield of unstable hybrid particles resulting from the insertion of foreign sequences and the "pre-existing immunity" problem due to the fact that the HBcAg is derived from a human pathogen have limited the development of this carrier technology. As a means of addressing the "pre-existing immunity" problem we have used the core proteins from the rodent hepdnaviruses. A number of advantages to the use of the rodent hepadnaviral core proteins as opposed to the HBcAg for vaccine design were defined including: equal or superior immunogenicity at the T and B cell levels the use of the rodent core proteins does not compromise the anti-HBc diagnostic assay; the efficacy of the rodent core proteins as vaccine carriers will not be limited by pre-existing anti-HBc antibodies that are present in previously and currently HBV-infected persons; and the HBcAg-specific tolerance present in HBV chronic carriers call be circumvented by the use of the rodent core proteins. (c) 2006 Elsevier Ltd. All rights reserved.