Characterization of a permissive epitope insertion site in adenovirus hexon
Characterization of a permissive epitope insertion site in adenovirus hexon
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DOI：
10.1128/jvi.00256-06
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发表时间：
2006-06-01
影响因子：
5.4
通讯作者：
Imperiale, Michael J.
中科院分区：
文献类型：
--
作者：
McConnell, Michael J.;Danthinne, Xavier;Imperiale, Michael J.
对腺病毒衣壳成分产生强大的免疫反应。特别地，针对六邻体蛋白引发了一种强有力且长期存在的不道德反应。这是由于抗原呈递细胞将腺病毒衣壳蛋白有效地呈递到CD4(+) T细胞，此外腺病毒衣壳的高度重复结构可以有效地刺激b细胞增殖。在目前的研究中，我们利用这种免疫反应，通过插入抗原表位，针对抗体反应的期望进入腺病毒六邻体。我们使用来自炭疽芽孢杆菌保护性抗原（PA）的b细胞表位作为模型抗原来表征六元体的高变区5 （HVR5）作为肽插入位点。我们证明HVR5可以容纳多达36个氨基酸的肽，而不会对病毒的感染性、生长或稳定性产生不利影响。含有嵌合六子的病毒在小鼠体内引发了针对PA的抗体，两次注射后总免疫球蛋白G （IgG）滴度约为1 × 10(3)。抗体反应包含IgG1和IgG2a亚型，表明Th1和Th2免疫已被刺激。野生型腺病毒和PA合成肽的共注射没有产生可检测到的抗体，这表明将表位结合到衣壳中对免疫刺激至关重要。总之，这些结果表明腺病毒衣壳是将b细胞表位呈递到免疫系统的有效载体，使其成为设计基于表位的疫苗的有用方法。
A robust immune response is generated against components of the adenovirus capsid. In particular, a potent and long-lived Immoral response is elicited against the hexon protein. This is due to the efficient presentation of adenovirus capsid proteins to CD4(+) T cells by antigen-presenting cells, in addition to the highly repetitive structure of the adenovirus capsids, which can efficiently stimulate B-cell proliferation. In the present study, we take advantage of this immune response by inserting epitopes against which an antibody response is desired into the adenovirus hexon. We use a B-cell epitope from Bacillus anthracis protective antigen (PA) as a model antigen to characterize hypervariable region 5 (HVR5) of hexon as a site for peptide insertion. We demonstrate that HVR5 can accommodate a peptide of up to 36 amino acids without adversely affecting virus infectivity, growth, or stability. Viruses containing chimeric hexons elicited antibodies against PA in mice, with total immunoglobulin G (IgG) titers reaching approximately 1 X 10(3) after two injections. The antibody response contained both IgG1 and IgG2a subtypes, suggesting that Th1 and Th2 immunity had been stimulated. Coinjection of wild-type adenovirus and a synthetic peptide from PA produced no detectable antibodies, indicating that incorporation of the epitope into the capsid was crucial for immune stimulation. Together, these results indicate that the adenovirus capsid is an efficient vehicle for presenting B-cell epitopes to the immune system, making this a useful approach for the design of epitope-based vaccines.