Immunogenicity of a novel DNA vaccine cassette expressing multiple human immunodeficiency virus (HIV-1) accessory genes

Immunogenicity of a novel DNA vaccine cassette expressing multiple human immunodeficiency virus (HIV-1) accessory genes
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表达多种人类免疫缺陷病毒 (HIV-1) 辅助基因的新型 DNA 疫苗盒的免疫原性

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发表时间:
2000
期刊:
AIDS (London)
影响因子:
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通讯作者:
D. Weiner
D. Weiner
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文献类型:
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作者:
V. Ayyavoo;S. Kudchodkar;M. Ramanathan;P. Le;K. Muthumani;Natesan Mani Megalai;T. Dentchev;Limaris Santiago;Conjeevaram Mrinalini;D. Weiner

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目的利用DNA疫苗方法研制HIV-1副基因免疫原。方法对shiv -1附属基因vif、vpu和nef进行修饰,使其在单个启动子的控制下表达,并在编码序列之间存在细胞蛋白水解裂解位点(vcn - p)。在小鼠中评估了这些构建体诱导的免疫反应。结果制备了表达Vif、Vpu和Nef的spdna疫苗构建体(pVVN-P),并对融合蛋白进行了适当的裂解。Vif、Vpu和Nef作为一种具有蛋白水解裂解位点(vcn - p)的融合蛋白能够诱导显著水平的细胞免疫应答。我们还观察到辅助基因Vif, Vpu和Nef (vpn - p)诱导了有效的T辅助1增殖反应,通过细胞因子的产生来测量。此外,pVVN-P表达盒能够在被感染的靶细胞中诱导针对多种HIV-1病毒的细胞毒性T淋巴细胞(CTL)反应。结论由B支附属基因构建的细胞介导的免疫应答可能对不同的HIV-1病毒有更广泛的识别,应该进一步研究针对HIV-1的预防和治疗性疫苗方案。
ObjectiveTo develop an HIV-1 accessory gene immunogen using a DNA vaccine approach. MethodsHIV-1 accessory genes vif, vpu and nef were modified to express under the control of a single promoter with cellular proteolytic cleavage sites between the coding sequences (VVN-P). Immune responses induced by these constructs were evaluated in mice. ResultsPDNA vaccine construct (pVVN-P) expressing Vif, Vpu and Nef was processed and the fusion protein was cleaved appropriately. Vif, Vpu and Nef as a fusion protein with proteolytic cleavage sites (VVN-P) is able to induce a significant level of cellular immune responses. We also observed that accessory genes Vif, Vpu and Nef (VVN-P) induced an effective T helper 1 proliferative response measured by cytokine production. Furthermore, expression cassette pVVN-P was able to induce cytotoxic T lymphocyte (CTL) responses against diverse HIV-1 viruses in infected target cells. ConclusionWe conclude that cell-mediated immune responses induced by accessory gene constructs from clade B may have a broader recognition of divergent HIV-1 viruses and should be further examined for both prophylactic and therapeutic vaccination schemes against HIV-1.
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