Novel conjugates of epitope fusion peptides with CpG-ODN display enhanced immunogenicity and HIV recognition
Novel conjugates of epitope fusion peptides with CpG-ODN display enhanced immunogenicity and HIV recognition
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DOI：
10.1016/j.vaccine.2005.01.093
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发表时间：
2005-05-16
期刊：
影响因子：
5.5
通讯作者：
Diamond, DJ
中科院分区：
文献类型：
--
作者：
Daftarian, P;Sharan, R;Diamond, DJ
疫苗接种策略仍然难以捉摸，有效对抗病毒性疾病病原体，但仍然足够温和，可供人类广泛使用。我们开发了一个模型系统，该系统依赖于识别来自HIV免疫显性抗原的特异性T细胞表位，以探索单链CpG-寡脱氧核苷酸（ODN）（CpG）作为佐剂。我们通过用CpG基序共价修饰表位融合肽来改进目前利用CpG与肽疫苗组合的策略。在人HLA A2的鼠模型中进行DNA-肽缀合物的免疫识别的表征。DNA-肽缀合物的免疫原性在对相同功能分子的非共价连接的混合物的敏感性方面是上级的，如通过肽介导的细胞毒性和IFN-γ释放以及针对病毒感染的保护所测量的。通过将DNA共价连接到表位肽来增强免疫识别的敏感性，作为HIV感染和其他感染性疾病的新型预防性疫苗策略应进一步评估。(c)2005爱思唯尔有限公司保留所有权利。
Vaccination strategies remain elusive that are effective against viral disease pathogens yet remain gentle enough for widespread human use. We developed a model system that relies on the recognition of specific T-cell epitopes from immunodominant antigens of HIV to explore single-stranded CpG-oligodeoxynucleotides (ODN) (CpG) as an adjuvant. We improved upon current strategies of utilizing CpG in combination with peptide vaccines by covalently modifying epitope fusion peptides with CpG motifs. Characterization of the immune recognition of DNA-peptide conjugates was carried out in a murine model of human HLA A2. Immunogenicity of DNA-peptide conjugates was superior in sensitivity to non-covalently linked mixtures of the same functional molecules as measured by peptide-mediated cytotoxicity and IFN-gamma release, as well as protection against viral infection. Enhancement of sensitivity of immune recognition by covalent attachment of DNA to epitope peptides should be further evaluated as a novel prophylactic vaccine strategy for HIV infection and other infectious diseases. (c) 2005 Elsevier Ltd. All rights reserved.