Selective induction of cell-mediated immunity and protection of rhesus macaques from chronic SHIVKU2 infection by prophylactic vaccination with a conserved HIV-1 envelope peptide-cocktail
Selective induction of cell-mediated immunity and protection of rhesus macaques from chronic SHIVKU2 infection by prophylactic vaccination with a conserved HIV-1 envelope peptide-cocktail
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DOI：
10.1016/j.virol.2007.08.022
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发表时间：
2008-01-05
期刊：
影响因子：
3.7
通讯作者：
Sastry, K. Jagannadha
中科院分区：
文献类型：
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作者：
Nehete, Pramod N.;Nehete, Bharti P.;Sastry, K. Jagannadha
通过猿猴人类免疫缺陷病毒（SHIV）感染印度起源的恒河猴被认为是用于基于HIV-1包膜直接测试候选疫苗的功效的合适的临床前模型。我们使用这种模型与肽鸡尾酒组成的高度保守的HIV-1包膜序列免疫原性/抗原性的猕猴和人类的预防性疫苗接种。分别使用自体树突状细胞（DC）和弗氏佐剂通过静脉内和皮下途径用肽混合物免疫各组猕猴。疫苗引起抗原特异性IFN-γ产生细胞和T细胞增殖，但不引起HIV中和抗体。接种疫苗的动物还表现出针对表达包膜蛋白的靶细胞的有效交叉进化枝细胞溶解活性，所述包膜蛋白对应于代表多个进化枝的HIV-1毒株，所述HIV-1毒株在用致病性SHIVKU 2静脉内攻击后增加。病毒中和抗体在对照组和接种疫苗的猴感染后检测不到或仅以低水平短暂存在。与模拟疫苗接种对照相比，大多数疫苗接种猴实现了血浆病毒血症的显著控制，导致检测不到水平。与弗氏佐剂相比，使用自体DC的肽混合物接种的猴子和免疫接种的动物显示出显著更高的IFN-γ产生、更高水平的疫苗特异性IFN-γ产生CD 4（+）细胞和显著的血浆病毒血症控制。这些结果支持基于DC的疫苗递送和保守的HIV-1包膜肽鸡尾酒的效用，其能够引发强细胞介导的免疫，用于潜在的包含在HIV疫苗接种策略中。(c)2007爱思唯尔公司All rights reserved.
Infection of Indian-origin rhesus macaques by the simian human immunodeficiency virus (SHIV) is considered to be a suitable preclinical model for directly testing efficacy of vaccine candidates based on the HIV-1 envelope. We used this model for prophylactic vaccination with a peptide-cocktail comprised of highly conserved HIV-1 envelope sequences immunogenic/antigenic in macaques and humans. Separate groups of macaques were immunized with the peptide-cocktail by intravenous and subcutaneous routes using autologous dendritic cells (DC) and Freund's adjuvant, respectively. The vaccine elicited antigen specific IFN-gamma-producing cells and T-cell proliferation, but not HIV-neutralizing antibodies. The vaccinated animals also exhibited efficient cross-clade cytolytic activity against target cells expressing envelope proteins corresponding to HIV-1 strains representative of multiple clades that increased after intravenous challenge with pathogenic SHIVKU2. Virus-neutralizing antibodies were either undetectable or present only transiently at low levels in the control as well as vaccinated monkeys after infection. Significant control of plasma viremia leading to undetectable levels was achieved in majority of vaccinated monkeys compared to mock-vaccinated controls. Monkeys vaccinated with the peptide-cocktail using autologous DC, compared to Freund's adjuvant, and the rnock-vaccinated animals, showed significantly higher IFN-gamma production, higher levels of vaccine-specific IFN-gamma producing CD4(+) cells and significant control of plasma viremia. These results support DC-based vaccine delivery and the utility of the conserved HIV-1 envelope peptide-cocktail, capable of priming strong cell-mediated immunity, for potential inclusion in HIV vaccination strategies. (c) 2007 Elsevier Inc. All rights reserved.