FOREIGN EPITOPES IN IMMUNODOMINANT REGIONS OF HEPATITIS-B CORE PARTICLES ARE HIGHLY IMMUNOGENIC AND CONFORMATIONALLY RESTRICTED
FOREIGN EPITOPES IN IMMUNODOMINANT REGIONS OF HEPATITIS-B CORE PARTICLES ARE HIGHLY IMMUNOGENIC AND CONFORMATIONALLY RESTRICTED
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DOI：
10.1016/0264-410x(91)90248-5
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发表时间：
1991-08-01
期刊：
影响因子：
5.5
通讯作者：
CLARKE, BE
中科院分区：
文献类型：
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作者：
BROWN, AL;FRANCIS, MJ;CLARKE, BE
利用人鼻病毒(HRV)的线性中和位点，研究了异源氨基酸序列在HBcAg颗粒表面的呈现。以前的工作表明，融合颗粒，其中HRV肽序列连接到HBcAg蛋白的氨基末端，在实验动物中诱导良好的免疫反应。利用HBcAg颗粒结构的预测模型和主要免疫原区的大致位置，我们设计和构建了指导嵌合颗粒合成的细菌表达载体，其中异源序列呈现在颗粒上的免疫优势区域内。与相同多肽序列与HBcAg的氨基末端融合相比，对异源多肽序列的免疫学反应至少提高了10倍。此外，通过HBcAg蛋白两端的连接对异源多肽施加的限制导致了更受限制的结构。在鼻病毒多肽序列的情况下，这导致了与天然病毒颗粒上的抗原构象更相似的抗原构象。这样的系统很好地为诱导针对特定表位的高滴度抗体提供了一种通用的方法。
The presentation of heterologous amino acid sequences on the surface of hepatitis B core antigen (HBcAg) particles has been studied using a defined linear neutralization site from human rhinovirus (HRV). Previous work has shown that fusion particles, in which the HRV peptide sequence is linked to the amino terminus of the HBcAg protein, induce excellent immune responses in experimental animals. Using predictive models of HBcAg particulate structure and the approximate location of the major immunogenic regions we have designed and constructed bacterial expression vectors which direct synthesis of chimeric particles in which heterologous sequences are presented within an immunodominant area on the particle. Immunological responses to the heterologous peptide sequence are improved by at least tenfold when compared with amino terminal fusions of the same peptide sequence to HBcAg. Moreover, the restriction placed on the heterologous peptide by its linkage at both ends within the HBcAg protein results in a more constrained structure. In the case of the rhinovirus peptide sequence this results in an antigenic conformation more closely resembling that on the native virus particle. Such a system lends itself well as a general approach to the induction of high titre antibodies against defined epitopes.