Lentivirus-like particles without reverse transcriptase elicit efficient immune responses.
Lentivirus-like particles without reverse transcriptase elicit efficient immune responses.
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DOI：
10.2174/157016206778560018
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发表时间：
2006-09
影响因子：
1
通讯作者：
Sean P Mcburney;K. Young;C. Nwaigwe;A. Soloff;K. Cole;T. Ross
中科院分区：
文献类型：
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作者：
Sean P Mcburney;K. Young;C. Nwaigwe;A. Soloff;K. Cole;T. Ross
在HIV或SIV感染后，逆转录酶（RT）指导单链RNA基因组转化为整合到宿主细胞基因组中的双链DNA分子。RT编码几种免疫原性表位，这些表位对于包含在用于HIV感染的人疫苗中是理想的，然而，安全性问题已经抑制了将酶活性RT分子包含在AIDS疫苗中的热情。在这项研究中，从DNA质粒表达病毒调节的，复制缺陷型慢病毒颗粒。缺失整合酶、Vpr、Vif、Nef和长末端重复序列（LTR）的序列，并将突变工程化到衣壳中以减少RNA包装。病毒样颗粒不包含RT（HIV-VLP DeltaRT或SHIV-VLP DeltaRT）或包含全长酶失活RT分子（HIV-VLP或SHIV-VLP）。每种分泌的VLP用源自灵长类细胞的脂质双层包封，所述脂质双层具有与感染性病毒体相似浓度的包埋的天然病毒包膜。在胞嘧啶-磷酸-鸟苷寡脱氧核苷酸（CpG ODN）的存在下，通过鼻内接种用纯化的VLP接种BALB/c小鼠（第0、3和6周）。所有的VLP，有或没有RT，引起了强大的体液和细胞免疫反应的Gag，Pol，和Env抗原。因此，RT的缺乏增强了这些VLP用于未来人类临床试验的安全性，而不会显著降低这些VLP免疫原的总体免疫原性。
Following infection by HIV or SIV, reverse transcriptase (RT) directs the conversion of the single-stranded RNA genome into a double-stranded DNA molecule that integrates into the host cell genome. RT encodes for several immunogenic epitopes that are desirable for inclusion in a human vaccine for HIV infection, however, issues of safety have dampened enthusiasm for inclusion of an enzymatically-active RT molecule into an AIDS vaccine. In this study, virally-regulated, replication-incompetent lentiviral particles were expressed from DNA plasmids. The sequences for integrase, Vpr, Vif, Nef, and the long terminal repeats (LTRs) were deleted and mutations were engineered into capsid to decreases RNA packaging. Virus-like particles incorporated no RT (HIV-VLP DeltaRT or SHIV-VLP DeltaRT) or contained a full-length enzymatically-inactivated RT molecule (HIV-VLP or SHIV-VLP). Each secreted VLP was enveloped with a lipid bilayer derived from primate cells with embedded, native viral envelopes in similar concentrations as infectious virions. BALB/c mice were vaccinated (weeks 0, 3, and 6) with purified VLPs via intranasal inoculation in the presence of cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs). All VLPs, with or without RT, elicited both robust humoral and cellular immune responses to Gag, Pol, and Env antigens. Therefore, the lack of RT enhances the safety of these VLPs for use in future human clinical trials without a significant reduction in the overall immunogenicity of these VLP immunogens.