Polyvalent HIV-1 Env vaccine formulations delivered by the DNA priming plus protein boosting approach are effective in generating neutralizing antibodies against primary human immunodeficiency virus type 1 isolates from subtypes A, B, C, D and E
Polyvalent HIV-1 Env vaccine formulations delivered by the DNA priming plus protein boosting approach are effective in generating neutralizing antibodies against primary human immunodeficiency virus type 1 isolates from subtypes A, B, C, D and E
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DOI：
10.1016/j.virol.2006.02.032
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发表时间：
2006-06-20
期刊：
影响因子：
3.7
通讯作者：
Lu, Shan
中科院分区：
文献类型：
--
作者：
Wang, Shixia;Pal, Ranajit;Lu, Shan
开发艾滋病毒-1疫苗的一个主要挑战是确定免疫原及其递送方法，这些免疫原及其递送方法可以引发针对不同遗传亚型初级分离株的广泛中和抗体。最近，我们证明了用表达原代HIV-1包膜糖蛋白（Env）的DNA疫苗进行引物，然后进行重组Env蛋白增强，成功地产生了针对不易中和的B支原代HIV-1分离物JR-FL的阳性中和抗体反应。在目前的研究中，我们研究了DNA引物加重组蛋白增强方法是否能够产生针对不同遗传亚型的HIV-1病毒分离株的中和抗体。首先用基因枪传递表达一种、三种或八种HIV-1 gp120原抗原的DNA疫苗免疫新西兰大白兔，然后增强重组gp120蛋白。中和抗体反应通过两个独立执行的中和试验来检验：第一个是针对10个HIV-1亚型a、13、C和E的原代分离株进行的单轮感染中和试验，第二个是针对12个来自a、B、C、D和E亚型表达HIV-1 Env原代抗原的假病毒以及来自MN和NL4-3病毒表达Env抗原的假病毒进行的表型检测。用DNA引物加蛋白增强方法免疫兔血清，而不是单独接种DNA疫苗或单独接种Env蛋白，在第一次试验中能够中和10种病毒中的7种，在第二次试验中能够中和14种病毒中的12种。更重要的是，用多价Env抗原免疫的血清能够比用单价抗原免疫的血清中和更高的病毒百分比。我们的研究结果表明，DNA引物和重组Env蛋白增强可用于递送基于Env抗原的多价HIV-1疫苗，以引发针对不同基因序列变异病毒的中和抗体反应。(c) 2006爱思唯尔公司版权所有。
A major challenge in developing an HIV-1 vaccine is to identify immunogens and their delivery methods that can elicit broad neutralizing antibodies against primary isolates of different genetic subtypes. Recently, we demonstrated that priming with DNA vaccines expressing primary HIV-1 envelope glycoprotein (Env) followed by recombinant Env protein boosting was successful in generating positive neutralizing antibody responses against a clade B primary HIV-1 isolate, JR-FL, that was not easily neutralized. In the current study, we examined whether the DNA priming plus recombinant protein boosting approach delivering a polyvalent primary Env formulation was able to generate neutralizing antibodies against primary HIV-1 viral isolates from various genetic subtypes. New Zealand White rabbits were first immunized with DNA vaccines expressing one, three or eight primary HIV-1 gp120 antigens delivered by a gene gun followed by recombinant gp120 protein boosting. Neutralizing antibody responses were examined by two independently executed neutralization assays: the first one was a single round infection neutralization assay against a panel of 10 primary HIV-1 isolates of subtypes A, 13, C and E and the second one used the PhenoSense assay against a panel of 12 pseudovirues expressing primary HIV-1 Env antigens from subtypes A, B, C, D and E as well as 2 pseudoviruses expressing the Env antigens from MN and NL4-3 viruses. Rabbit sera immunized with the DNA priming plus protein boosting approach, but not DNA vaccine alone or Env protein alone, were capable of neutralizing 7 of 10 viruses in the first assay and 12 of 14 viruses in the second assay. More importantly, sera immunized with the polyvalent Env antigens were able to neutralize a significantly higher percentage of viruses than the sera immunized with the monovalent antigens. Our results suggest that DNA priming followed by recombinant Env protein boosting can be used to deliver polyvalent Env-antigen-based HIV-1 vaccines to elicit neutralizing antibody responses against viruses with diverse genetic sequence variations. (c) 2006 Elsevier Inc. All rights reserved.