Protection by dendritic cells-based HIV synthetic peptide cocktail vaccine: preclinical studies in the SHIV-rhesus model

Protection by dendritic cells-based HIV synthetic peptide cocktail vaccine: preclinical studies in the SHIV-rhesus model
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DOI:
10.1016/j.vaccine.2005.01.052
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发表时间:
2005-03-18
期刊:
影响因子:
5.5
通讯作者:
Sastry, KJ
Sastry, KJ
中科院分区:
医学3区
文献类型:
--
作者:
Nehete, PN;Nehete, BP;Sastry, KJ

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由于HIV-1病毒的高突变率,以及在动物模型中直接测试HIV抗原以辨别保护性免疫的性质的局限性,针对HIV-1的疫苗开发工作受到阻碍。我们开发了一种由高度保守的HIV包膜肽混合物组成的多价疫苗,该疫苗专注于引发抗原特异性辅助T细胞和CTL应答。在这里,我们报告保护恒河猴对致病性SHIV89.6P的挑战,通过启动细胞介导的免疫与树突状细胞提供的肽鸡尾酒预防性接种。与模拟接种或使用IFA用肽混合物免疫的猴子相比,用肽混合物脉冲的DC接种显示出对AIDS相关死亡率的显著保护,并将血浆病毒血症降低至不可检测的水平。(c)2005爱思唯尔有限公司保留所有权利。
Vaccine development efforts against HIV-1 have been hindered because of the high mutation rate of the virus, and limitations for direct testing of HIV antigens in animal models to discern the nature of protective immunity. We developed a multivalent vaccine comprised of highly conserved HIV envelope peptide cocktail focused on priming antigen-specific helper T cell and CTL responses. Here we report protection of rhesus macaques against pathogenic SHIV89.6P challenge through priming cell-mediated immunity by prophylactic vaccination with the peptide-cocktail delivered by dendritic cells. Compared to monkeys mock-vaccinated or immunized with the peptide cocktail using IFA, vaccination with peptide cocktail-pulsed DC showed significant protection from AIDS-associated mortality and reduction in plasma viremia to undetectable levels. (c) 2005 Elsevier Ltd. All rights reserved.