Comparative ability of plasmid IL-12 and IL-15 to enhance cellular and humoral immune responses elicited by a SIVgag plasmid DNA vaccine and alter disease progression following SHIV89.6P challenge in rhesus macaques
Comparative ability of plasmid IL-12 and IL-15 to enhance cellular and humoral immune responses elicited by a SIVgag plasmid DNA vaccine and alter disease progression following SHIV89.6P challenge in rhesus macaques
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DOI：
10.1016/j.vaccine.2006.11.070
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发表时间：
2007-06-21
期刊：
影响因子：
5.5
通讯作者：
Israel, Zimra R.
中科院分区：
文献类型：
--
作者：
Chong, Siew-Yen;Egan, Michael A.;Israel, Zimra R.
已经证明基于质粒的IL-12成功地增强了DNA疫苗的免疫原性，从而能够减少免疫所需的DNA量。IL-15被认为影响CD 8（+）记忆T细胞的维持和增强效应子功能。由于引发长期记忆应答的能力是预防性疫苗的理想属性，我们试图评估这些基于质粒的细胞因子在恒河猴中用作疫苗佐剂的能力。用编码SIVgag的质粒DNA与质粒IL-12、IL-15或IL-12和IL-15的组合免疫猕猴。监测基于质粒的细胞因子增强SIVgag特异性细胞和体液免疫应答以及改变致病性SHIV89.6P攻击后的临床结果的能力。与单独接受SIVgag pDNA的猕猴相比，接受SIVgag pDNA与单独的质粒IL-12组合或与质粒IL-12和IL-15组合的猕猴表现出显著升高的细胞介导的和体液免疫应答，导致病毒攻击后改善的临床结果。接受SIVgag pDNA与单独的质粒IL-15组合的猕猴表现出细胞介导的和体液免疫应答的轻微增加，然而，病毒攻击后的临床结果没有改善。这些结果对于继续开发用于预防HIV-1感染的质粒DNA疫苗具有重要意义。(c)2007爱思唯尔有限公司保留所有权利。
Plasmid-based IL-12 has been demonstrated to successfully enhance the immunogenicity of DNA vaccines, thus enabling a reduction of the amount of DNA required for immunization. IL-15 is thought to affect the maintenance and enhance effector function of CD8(+) memory T cells. Since the ability to elicit a long-term memory response is a desirable attribute of a prophylactic vaccine, we sought to evaluate the ability of these plasmid-based cytokines to serve as vaccine adjuvants in rhesus macaques. Macaques were immunized with plasmid DNA encoding SIVgag in combination with plasmid IL-12, IL-15, or a combination of IL-12 and IL-15. The plasmid-based cytokines were monitored for their ability to augment SIVgag-specific cellular and humoral immune responses and to alter the clinical outcome following pathogenic SHIV89.6P challenge. Macaques receiving SIVgag pDNA in combination with plasmid IL-12 alone, or in combination with plasmid IL-12 and IL-15, demonstrated significantly elevated cell-mediated and humoral immune responses resulting in an improved clinical outcome following virus challenge compared to macaques receiving SIVgag pDNA alone. Macaques receiving SIVgag pDNA in combination with plasmid IL-15 alone demonstrated minor increases in cell-mediated and humoral immune responses, however, the clinical outcome following virus challenge was not improved. These results have important implications for the continued development of plasmid DNA vaccines for the prevention of HIV-1 infection. (c) 2007 Elsevier Ltd. All rights reserved.